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M.P. Zanin
School of Public Health, The University of Hong Kong, Hong Kong, China

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Review
Published: 19 July 2021 in Viruses
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The induction of a specific antibody response has long been accepted as a serological hallmark of recent infection or antigen exposure. Much of our understanding of the influenza antibody response has been derived from studying antibodies that target the hemagglutinin (HA) protein. However, growing evidence points to limitations associated with this approach. In this review, we aim to highlight the issue of antibody non-responsiveness after influenza virus infection and vaccination. We will then provide an overview of the major factors known to influence antibody responsiveness to influenza after infection and vaccination. We discuss the biological factors such as age, sex, influence of prior immunity, genetics, and some chronic infections that may affect the induction of influenza antibody responses. We also discuss the technical factors, such as assay choices, strain variations, and viral properties that may influence the sensitivity of the assays used to measure influenza antibodies. Understanding these factors will hopefully provide a more comprehensive picture of what influenza immunogenicity and protection means, which will be important in our effort to improve influenza vaccines.

ACS Style

Xia Lin; Fangmei Lin; Tingting Liang; Mariette Ducatez; Mark Zanin; Sook-San Wong. Antibody Responsiveness to Influenza: What Drives It? Viruses 2021, 13, 1400 .

AMA Style

Xia Lin, Fangmei Lin, Tingting Liang, Mariette Ducatez, Mark Zanin, Sook-San Wong. Antibody Responsiveness to Influenza: What Drives It? Viruses. 2021; 13 (7):1400.

Chicago/Turabian Style

Xia Lin; Fangmei Lin; Tingting Liang; Mariette Ducatez; Mark Zanin; Sook-San Wong. 2021. "Antibody Responsiveness to Influenza: What Drives It?" Viruses 13, no. 7: 1400.

Review
Published: 06 April 2021 in Viruses
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Hemagglutinin and neuraminidase, which constitute the glycoprotein spikes expressed on the surface of influenza A and B viruses, are the most exposed parts of the virus and play critical roles in the viral lifecycle. As such, they make prominent targets for the immune response and antiviral drugs. Neuraminidase inhibitors, particularly oseltamivir, constitute the most commonly used antivirals against influenza viruses, and they have proved their clinical utility against seasonal and emerging influenza viruses. However, the emergence of resistant strains remains a constant threat and consideration. Antivirals targeting the hemagglutinin protein are relatively new and have yet to gain global use but are proving to be effective additions to the antiviral repertoire, with a relatively high threshold for the emergence of resistance. Here we review antiviral drugs, both approved for clinical use and under investigation, that target the influenza virus hemagglutinin and neuraminidase proteins, focusing on their mechanisms of action and the emergence of resistance to them.

ACS Style

Yaqin Bai; Jeremy Jones; Sook-San Wong; Mark Zanin. Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance. Viruses 2021, 13, 624 .

AMA Style

Yaqin Bai, Jeremy Jones, Sook-San Wong, Mark Zanin. Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance. Viruses. 2021; 13 (4):624.

Chicago/Turabian Style

Yaqin Bai; Jeremy Jones; Sook-San Wong; Mark Zanin. 2021. "Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance." Viruses 13, no. 4: 624.

Short article
Published: 25 August 2020 in Influenza and Other Respiratory Viruses
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To inform seroepidemiological studies, we characterized the IgG‐ responses in COVID‐19 patients against the two major SARS‐CoV‐2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID‐19 sera collected up to 85 days post‐symptom onset and 230 non‐COVID‐19 sera, including 27 SARS sera from 2003. Although the average SARS‐CoV‐2 S and N‐IgG titers were comparable, N‐responses were more variable among individuals. S‐ and N‐assay specificity tested with non‐COVID‐19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross‐reactive potential and its' more consistent frequency of detection compared to N.

ACS Style

Cheng Xiao; Shiman Ling; Minshan Qiu; Zhenxuan Deng; Liping Chen; Airu Zhu; Yi Chen; Yong Liu; Xia Lin; Fangmei Lin; Qiubao Wu; Lihan Shen; Feng Ye; Xiaoqing Liu; Yimin Li; Jincun Zhao; Zifeng Yang; Benjamin J. Cowling; Richard Webby; Mark Zanin; Sook‐San Wong. Human post‐infection serological response to the spike and nucleocapsid proteins of SARS‐CoV‐2. Influenza and Other Respiratory Viruses 2020, 15, 7 -12.

AMA Style

Cheng Xiao, Shiman Ling, Minshan Qiu, Zhenxuan Deng, Liping Chen, Airu Zhu, Yi Chen, Yong Liu, Xia Lin, Fangmei Lin, Qiubao Wu, Lihan Shen, Feng Ye, Xiaoqing Liu, Yimin Li, Jincun Zhao, Zifeng Yang, Benjamin J. Cowling, Richard Webby, Mark Zanin, Sook‐San Wong. Human post‐infection serological response to the spike and nucleocapsid proteins of SARS‐CoV‐2. Influenza and Other Respiratory Viruses. 2020; 15 (1):7-12.

Chicago/Turabian Style

Cheng Xiao; Shiman Ling; Minshan Qiu; Zhenxuan Deng; Liping Chen; Airu Zhu; Yi Chen; Yong Liu; Xia Lin; Fangmei Lin; Qiubao Wu; Lihan Shen; Feng Ye; Xiaoqing Liu; Yimin Li; Jincun Zhao; Zifeng Yang; Benjamin J. Cowling; Richard Webby; Mark Zanin; Sook‐San Wong. 2020. "Human post‐infection serological response to the spike and nucleocapsid proteins of SARS‐CoV‐2." Influenza and Other Respiratory Viruses 15, no. 1: 7-12.

Journal article
Published: 06 July 2020 in Viruses
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The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) mice are more susceptible to influenza virus A/PR/8/1934 (H1N1) infection than their wild type (WT) counterparts. The KO mice lost weight faster than the WT mice and, unlike WT mice, could not recover their original body weight. Consequently, more KO mice succumbed to infection, which corresponded with higher lung viral loads. Conversely, the expression of the critical innate antiviral response genes interferon alpha/beta, CD80, CXCL10 and IL15 was significantly downregulated in KO mouse lungs compared to WT mouse lungs. These data are consistent with the known function of HDAC6 of de-acetylating the retinoic acid inducible gene-I (RIG-I) and activating the host innate antiviral response cascade. Loss of HDAC6 thus leads to a blunted innate response and increased susceptibility of mice to influenza A virus infection.

ACS Style

Mark Zanin; Jennifer DeBeauchamp; Gowthami Vangala; Richard J. Webby; Matloob Husain. Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection. Viruses 2020, 12, 728 .

AMA Style

Mark Zanin, Jennifer DeBeauchamp, Gowthami Vangala, Richard J. Webby, Matloob Husain. Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection. Viruses. 2020; 12 (7):728.

Chicago/Turabian Style

Mark Zanin; Jennifer DeBeauchamp; Gowthami Vangala; Richard J. Webby; Matloob Husain. 2020. "Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection." Viruses 12, no. 7: 728.

Original article
Published: 24 June 2020 in Influenza and Other Respiratory Viruses
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Background Severe COVID‐19 patients typically test positive for SARS‐CoV‐2 RNA for extended periods of time, even after recovery from severe disease. Due to the timeframe involved, these patients may have developed humoral immunity to SARS‐CoV‐2 while still testing positive for viral RNA in swabs. Data are lacking on exposure risks in these situations. Here, we studied SARS‐CoV‐2 environmental contamination in an ICU and an isolation ward caring for such COVID‐19 patients. Methods We collected air and surface samples in a hospital caring for critical and severe COVID‐19 cases from common areas and areas proximal to patients. Results Of the 218 ICU samples, an air sample contained SARS‐CoV‐2 RNA. Of the 182 isolation ward samples, nine contained SARS‐CoV‐2 RNA. These were collected from a facemask, the floor, mobile phones, and the air in the patient room and bathroom. Serum antibodies against SARS‐CoV‐2 were detected in these patients at the beginning of the study. Conclusions While there is a perception of increased risk in the ICU, our study demonstrates that isolation wards may pose greater risks to healthcare workers and exposure risks remain with clinically improved patients, weeks after their initial diagnoses. As these patients had serum antibodies, further studies may be warranted to study the utility of serum antibodies as a surrogate of viral clearance in allowing people to return to work. We recommend continued vigilance even with patients who appear to have recovered from COVID‐19.

ACS Style

Hui Lei; Feng Ye; Xiaoqing Liu; Zhenting Huang; Shiman Ling; Zhanpeng Jiang; Jing Cheng; Xiaoqun Huang; Qiubao Wu; Shiguan Wu; Yanmin Xie; Cheng Xiao; Dan Ye; Zifeng Yang; Yimin Li; Nancy H. L. Leung; Benjamin J. Cowling; Jianxing He; Sook‐San Wong; Mark Zanin. SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients. Influenza and Other Respiratory Viruses 2020, 14, 688 -699.

AMA Style

Hui Lei, Feng Ye, Xiaoqing Liu, Zhenting Huang, Shiman Ling, Zhanpeng Jiang, Jing Cheng, Xiaoqun Huang, Qiubao Wu, Shiguan Wu, Yanmin Xie, Cheng Xiao, Dan Ye, Zifeng Yang, Yimin Li, Nancy H. L. Leung, Benjamin J. Cowling, Jianxing He, Sook‐San Wong, Mark Zanin. SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients. Influenza and Other Respiratory Viruses. 2020; 14 (6):688-699.

Chicago/Turabian Style

Hui Lei; Feng Ye; Xiaoqing Liu; Zhenting Huang; Shiman Ling; Zhanpeng Jiang; Jing Cheng; Xiaoqun Huang; Qiubao Wu; Shiguan Wu; Yanmin Xie; Cheng Xiao; Dan Ye; Zifeng Yang; Yimin Li; Nancy H. L. Leung; Benjamin J. Cowling; Jianxing He; Sook‐San Wong; Mark Zanin. 2020. "SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients." Influenza and Other Respiratory Viruses 14, no. 6: 688-699.

Journal article
Published: 08 April 2020 in European Respiratory Journal
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BackgroundDuring the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.MethodsCollaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined.ResultsAt the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05–2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40–1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01–1.08)).ConclusionThere were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

ACS Style

Wen-Hua Liang; Wei-Jie Guan; Caichen Li; Yi-Min Li; Heng-Rui Liang; Yi Zhao; Xiao-Qing Liu; Ling Sang; Ru-Chong Chen; Chun-Li Tang; Tao Wang; Wei Wang; Qi-Hua He; Zi-Sheng Chen; Sook-San Wong; Mark Zanin; Jun Liu; Xin Xu; Jun Huang; Jian-Fu Li; Li-Min Ou; Bo Cheng; Shan Xiong; Zhan-Hong Xie; Zheng-Yi Ni; Yu Hu; Lei Liu; Hong Shan; Chun-Liang Lei; Yi-Xiang Peng; Li Wei; Yong Liu; Ya-Hua Hu; Peng Peng; Jian-Ming Wang; Ji-Yang Liu; Zhong Chen; Gang Li; Zhi-Jian Zheng; Shao-Qin Qiu; Jie Luo; Chang-Jiang Ye; Shao-Yong Zhu; Lin-Ling Cheng; Feng Ye; Shi-Yue Li; Jin-Ping Zheng; Nuo-Fu Zhang; Nan-Shan Zhong; Jian-Xing He. Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China. European Respiratory Journal 2020, 55, 2000562 .

AMA Style

Wen-Hua Liang, Wei-Jie Guan, Caichen Li, Yi-Min Li, Heng-Rui Liang, Yi Zhao, Xiao-Qing Liu, Ling Sang, Ru-Chong Chen, Chun-Li Tang, Tao Wang, Wei Wang, Qi-Hua He, Zi-Sheng Chen, Sook-San Wong, Mark Zanin, Jun Liu, Xin Xu, Jun Huang, Jian-Fu Li, Li-Min Ou, Bo Cheng, Shan Xiong, Zhan-Hong Xie, Zheng-Yi Ni, Yu Hu, Lei Liu, Hong Shan, Chun-Liang Lei, Yi-Xiang Peng, Li Wei, Yong Liu, Ya-Hua Hu, Peng Peng, Jian-Ming Wang, Ji-Yang Liu, Zhong Chen, Gang Li, Zhi-Jian Zheng, Shao-Qin Qiu, Jie Luo, Chang-Jiang Ye, Shao-Yong Zhu, Lin-Ling Cheng, Feng Ye, Shi-Yue Li, Jin-Ping Zheng, Nuo-Fu Zhang, Nan-Shan Zhong, Jian-Xing He. Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China. European Respiratory Journal. 2020; 55 (6):2000562.

Chicago/Turabian Style

Wen-Hua Liang; Wei-Jie Guan; Caichen Li; Yi-Min Li; Heng-Rui Liang; Yi Zhao; Xiao-Qing Liu; Ling Sang; Ru-Chong Chen; Chun-Li Tang; Tao Wang; Wei Wang; Qi-Hua He; Zi-Sheng Chen; Sook-San Wong; Mark Zanin; Jun Liu; Xin Xu; Jun Huang; Jian-Fu Li; Li-Min Ou; Bo Cheng; Shan Xiong; Zhan-Hong Xie; Zheng-Yi Ni; Yu Hu; Lei Liu; Hong Shan; Chun-Liang Lei; Yi-Xiang Peng; Li Wei; Yong Liu; Ya-Hua Hu; Peng Peng; Jian-Ming Wang; Ji-Yang Liu; Zhong Chen; Gang Li; Zhi-Jian Zheng; Shao-Qin Qiu; Jie Luo; Chang-Jiang Ye; Shao-Yong Zhu; Lin-Ling Cheng; Feng Ye; Shi-Yue Li; Jin-Ping Zheng; Nuo-Fu Zhang; Nan-Shan Zhong; Jian-Xing He. 2020. "Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China." European Respiratory Journal 55, no. 6: 2000562.

Journal article
Published: 01 March 2020 in Journal of Thoracic Disease
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Background: The coronavirus disease 2019 (COVID-19) outbreak originating in Wuhan, Hubei province, China, coincided with chunyun, the period of mass migration for the annual Spring Festival. To contain its spread, China adopted unprecedented nationwide interventions on January 23 2020. These policies included large-scale quarantine, strict controls on travel and extensive monitoring of suspected cases. However, it is unknown whether these policies have had an impact on the epidemic. We sought to show how these control measures impacted the containment of the epidemic. Methods: We integrated population migration data before and after January 23 and most updated COVID-19 epidemiological data into the Susceptible-Exposed-Infectious-Removed (SEIR) model to derive the epidemic curve. We also used an artificial intelligence (AI) approach, trained on the 2003 SARS data, to predict the epidemic. Results: We found that the epidemic of China should peak by late February, showing gradual decline by end of April. A five-day delay in implementation would have increased epidemic size in mainland China three-fold. Lifting the Hubei quarantine would lead to a second epidemic peak in Hubei province in mid-March and extend the epidemic to late April, a result corroborated by the machine learning prediction. Conclusions: Our dynamic SEIR model was effective in predicting the COVID-19 epidemic peaks and sizes. The implementation of control measures on January 23 2020 was indispensable in reducing the eventual COVID-19 epidemic size.

ACS Style

Zifeng Yang; Zhiqi Zeng; Ke Wang; Sook-San Wong; Wenhua Liang; Mark Zanin; Peng Liu; Xudong Cao; Zhongqiang Gao; Zhitong Mai; Jingyi Liang; Xiaoqing Liu; Shiyue Li; Yimin Li; Feng Ye; Weijie Guan; Yifan Yang; Fei Li; Shengmei Luo; Yuqi Xie; Bin Liu; Zhoulang Wang; Shaobo Zhang; YaoNan Wang; Nanshan Zhong; Jianxing He. Modified SEIR and AI prediction of the epidemics trend of COVID-19 in China under public health interventions. Journal of Thoracic Disease 2020, 12, 165 -174.

AMA Style

Zifeng Yang, Zhiqi Zeng, Ke Wang, Sook-San Wong, Wenhua Liang, Mark Zanin, Peng Liu, Xudong Cao, Zhongqiang Gao, Zhitong Mai, Jingyi Liang, Xiaoqing Liu, Shiyue Li, Yimin Li, Feng Ye, Weijie Guan, Yifan Yang, Fei Li, Shengmei Luo, Yuqi Xie, Bin Liu, Zhoulang Wang, Shaobo Zhang, YaoNan Wang, Nanshan Zhong, Jianxing He. Modified SEIR and AI prediction of the epidemics trend of COVID-19 in China under public health interventions. Journal of Thoracic Disease. 2020; 12 (3):165-174.

Chicago/Turabian Style

Zifeng Yang; Zhiqi Zeng; Ke Wang; Sook-San Wong; Wenhua Liang; Mark Zanin; Peng Liu; Xudong Cao; Zhongqiang Gao; Zhitong Mai; Jingyi Liang; Xiaoqing Liu; Shiyue Li; Yimin Li; Feng Ye; Weijie Guan; Yifan Yang; Fei Li; Shengmei Luo; Yuqi Xie; Bin Liu; Zhoulang Wang; Shaobo Zhang; YaoNan Wang; Nanshan Zhong; Jianxing He. 2020. "Modified SEIR and AI prediction of the epidemics trend of COVID-19 in China under public health interventions." Journal of Thoracic Disease 12, no. 3: 165-174.

Journal article
Published: 07 June 2019 in Virology Journal
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Influenza B virus is a main causative pathogen of annual influenza epidemics, however, research on influenza B virus in general lags behind that on influenza A viruses, one of the important reasons is studies on influenza B viruses in animal models are limited. Here we investigated the tree shrew as a potential model for influenza B virus studies. Tree shrews and ferrets were inoculated with either a Yamagata or Victoria lineage influenza B virus. Symptoms including nasal discharge and weight loss were observed. Nasal wash and respiratory tissues were collected at 2, 4 and 6 days post inoculation (DPI). Viral titers were measured in nasal washes and tissues were used for pathological examination and extraction of mRNA for measurement of cytokine expression. Clinical signs and pathological changes were also evident in the respiratory tracts of tree shrews and ferrets. Although nasal symptoms including sneezing and rhinorrhea were evident in ferrets infected with influenza B virus, tree shrews showed no significant respiratory symptoms, only milder nasal secretions appeared. Weight loss was observed in tree shrews but not ferrets. V0215 and Y12 replicated in all three animal (ferrets, tree shrews and mice) models with peak titers evident on 2DPI. There were no significant differences in peak viral titers in ferrets and tree shrews inoculated with Y12 at 2 and 4DPI, but viral titers were detected at 6DPI in tree shrews. Tree shrews infected with influenza B virus showed similar seroconversion and respiratory tract pathology to ferrets. Elevated levels of cytokines were detected in the tissues isolated from the respiratory tract after infection with either V0215 or Y12 compared to the levels in the uninfected control in both animals. Overall, the tree shrew was sensitive to infection and disease by influenza B virus. The tree shrew to be a promising model for influenza B virus research.

ACS Style

Bing Yuan; Chunguang Yang; Xueshan Xia; Mark Zanin; Sook-San Wong; Fan Yang; Jixiang Chang; Zhitong Mai; Jin Zhao; Yunhui Zhang; Runfeng Li; Nanshan Zhong; Zifeng Yang. The tree shrew is a promising model for the study of influenza B virus infection. Virology Journal 2019, 16, 77 .

AMA Style

Bing Yuan, Chunguang Yang, Xueshan Xia, Mark Zanin, Sook-San Wong, Fan Yang, Jixiang Chang, Zhitong Mai, Jin Zhao, Yunhui Zhang, Runfeng Li, Nanshan Zhong, Zifeng Yang. The tree shrew is a promising model for the study of influenza B virus infection. Virology Journal. 2019; 16 (1):77.

Chicago/Turabian Style

Bing Yuan; Chunguang Yang; Xueshan Xia; Mark Zanin; Sook-San Wong; Fan Yang; Jixiang Chang; Zhitong Mai; Jin Zhao; Yunhui Zhang; Runfeng Li; Nanshan Zhong; Zifeng Yang. 2019. "The tree shrew is a promising model for the study of influenza B virus infection." Virology Journal 16, no. 1: 77.

Original article
Published: 15 January 2019 in Journal of Neurochemistry
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Sphingosine‐1‐phosphate (S1P) is an essential bioactive sphingosine lipid involved in many neurological disorders. Sphingosine kinase 1 (SphK1), a key enzyme for S1P production, is concentrated in presynaptic terminals. However, the role of S1P/SphK1 signaling in exocytosis remains elusive. By detecting catecholamine release from single vesicles in chromaffin cells, we show that a dominant negative SphK1 (SphK1DN ) reduces the number of amperometric spikes and increases the duration of foot, which reflects release through a fusion pore, implying critical roles for S1P in regulating the rate of exocytosis and fusion pore expansion. Similar phenotypes were observed in chromaffin cells obtained from SphK1 knockout mice compared to those from wild‐type mice. In addition, extracellular S1P treatment increased the number of amperometric spikes, and this increase, in turn, was inhibited by a selective S1P3 receptor blocker, suggesting extracellular S1P may regulate the rate of exocytosis via activation of S1P3. Furthermore, intracellular S1P application induced a decrease in foot duration of amperometric spikes in control cells, indicating intracellular S1P may regulate fusion pore expansion during exocytosis. Taken together, our study represents the first demonstration that S1P regulates exocytosis through distinct mechanisms: extracellular S1P may modulate the rate of exocytosis via activation of S1P receptors while intracellular S1P may directly control fusion pore expansion during exocytosis. Open science badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

ACS Style

Zhong‐Jiao Jiang; Taylor L. Delaney; Mark Zanin; Rainer V. Haberberger; Stuart Pitson; Jian Huang; Simon Alford; Stephanie M. Cologna; Damien J. Keating; Liang‐Wei Gong. Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells. Journal of Neurochemistry 2019, 149, 729 -746.

AMA Style

Zhong‐Jiao Jiang, Taylor L. Delaney, Mark Zanin, Rainer V. Haberberger, Stuart Pitson, Jian Huang, Simon Alford, Stephanie M. Cologna, Damien J. Keating, Liang‐Wei Gong. Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells. Journal of Neurochemistry. 2019; 149 (6):729-746.

Chicago/Turabian Style

Zhong‐Jiao Jiang; Taylor L. Delaney; Mark Zanin; Rainer V. Haberberger; Stuart Pitson; Jian Huang; Simon Alford; Stephanie M. Cologna; Damien J. Keating; Liang‐Wei Gong. 2019. "Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells." Journal of Neurochemistry 149, no. 6: 729-746.

Review
Published: 01 July 2018 in Journal of Thoracic Disease
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Despite major advances in medicine, infectious diseases still pose a significant threat to humanity. Mammalian models of disease have proved extremely useful in adding to the understanding of infectious diseases and the development of prophylactic and/or therapeutic interventions. Arguably the most important considerations of any animal model are (I) the similarity of the model to humans with respect to anatomy, physiology, immunology and disease progression, and (II) the expense of conducting experiments using the model organism. Often the choice of a model represents a compromise between these factors. Here we review the Northern Tree shrew ( Tupaia belangeri ), or tupaia, as a useful model for the study of infectious diseases. Tupaias are non-human primates similar in size to squirrels that are indigenous to Asia. Their genome has been sequenced and, overall, shows relatively high similarity to humans. There is also a close homology of many aspects of tupaia biology with human biology. Importantly, from an infectious diseases viewpoint, tupaias are susceptible to infection with unadapted human pathogens and manifest clinical signs akin to human infections. Overall, the relatively small size of the tupaia, their homology to humans and their susceptibility to human pathogens make them a useful model for the study of infectious diseases.

ACS Style

Runfeng Li; Mark Zanin; Xueshan Xia; Zifeng Yang. The tree shrew as a model for infectious diseases research. Journal of Thoracic Disease 2018, 10, S2272 -S2279.

AMA Style

Runfeng Li, Mark Zanin, Xueshan Xia, Zifeng Yang. The tree shrew as a model for infectious diseases research. Journal of Thoracic Disease. 2018; 10 (19):S2272-S2279.

Chicago/Turabian Style

Runfeng Li; Mark Zanin; Xueshan Xia; Zifeng Yang. 2018. "The tree shrew as a model for infectious diseases research." Journal of Thoracic Disease 10, no. 19: S2272-S2279.

Journal article
Published: 05 September 2017 in Proceedings of the National Academy of Sciences
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North American wild birds are an important reservoir of influenza A viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood. Our surveillance of avian influenza viruses (AIVs) at Delaware Bay, USA, revealed a group of similar H1N1 AIVs isolated in 2009, some of which were airborne-transmissible in the ferret model without prior adaptation. Comparison of the genomes of these viruses revealed genetic markers of airborne transmissibility in the Polymerase Basic 2 (PB2), PB1, PB1-F2, Polymerase Acidic-X (PA-X), Nonstructural Protein 1 (NS1), and Nuclear Export Protein (NEP) genes. We studied the role of NS1 in airborne transmission and found that NS1 mutants that were not airborne-transmissible caused limited tissue pathology in the upper respiratory tract (URT). Viral maturation was also delayed, evident as strong intranuclear staining and little virus at the mucosa. Our study of this naturally occurring constellation of genetic markers has provided insights into the poorly understood phenomenon of AIV airborne transmissibility by revealing a role for NS1 and characteristics of viral replication in the URT that were associated with airborne transmission. The transmissibility of these viruses further highlights the pandemic potential of AIVs in the wild bird reservoir and the need to maintain surveillance.

ACS Style

Mark Zanin; Sook-San Wong; Subrata Barman; Challika Kaewborisuth; Peter Vogel; Adam Rubrum; Daniel Darnell; Atanaska Marinova-Petkova; Scott Krauss; Richard J. Webby; Robert G. Webster. Molecular basis of mammalian transmissibility of avian H1N1 influenza viruses and their pandemic potential. Proceedings of the National Academy of Sciences 2017, 114, 11217 -11222.

AMA Style

Mark Zanin, Sook-San Wong, Subrata Barman, Challika Kaewborisuth, Peter Vogel, Adam Rubrum, Daniel Darnell, Atanaska Marinova-Petkova, Scott Krauss, Richard J. Webby, Robert G. Webster. Molecular basis of mammalian transmissibility of avian H1N1 influenza viruses and their pandemic potential. Proceedings of the National Academy of Sciences. 2017; 114 (42):11217-11222.

Chicago/Turabian Style

Mark Zanin; Sook-San Wong; Subrata Barman; Challika Kaewborisuth; Peter Vogel; Adam Rubrum; Daniel Darnell; Atanaska Marinova-Petkova; Scott Krauss; Richard J. Webby; Robert G. Webster. 2017. "Molecular basis of mammalian transmissibility of avian H1N1 influenza viruses and their pandemic potential." Proceedings of the National Academy of Sciences 114, no. 42: 11217-11222.

Journal article
Published: 08 June 2017 in npj Vaccines
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Conventional inactivated avian influenza vaccines have performed poorly in past vaccine trials, leading to the hypothesis that they are less immunogenic than seasonal influenza vaccines. We tested this hypothesis by comparing the immunogenicity of the H5N1 and H7N9 vaccines (avian influenza vaccines) to a seasonal trivalent inactivated influenza vaccine in naïve ferrets, administered with or without the adjuvants MF59 or AS03. Vaccine immunogenicity was assessed by measuring neutralizing antibody titers against hemagglutinin and neuraminidase and by hemagglutinin -specific IgG levels. Two doses of unadjuvanted vaccines induced low or no HA-specific IgG responses and hemagglutination-inhibiting titers. Adjuvanted vaccines induced comparable IgG-titers, but poorer neutralizing antibody titers for the H5 vaccine. All adjuvanted vaccines elicited detectable anti- neuraminidase -antibodies with the exception of the H5N1 vaccine, likely due to the low amounts of neuraminidase in the vaccine. Overall, the H5N1 vaccine had poorer capacity to induce neutralizing antibodies, but not HA-specific IgG, compared to H7N9 or trivalent inactivated influenza vaccine. Evidence shows that vaccines for avian flu provoke a poorer immune response than those for seasonal human flu. Avian influenza is an emergent disease that poses a credible threat to public health, yet vaccines to treat avian flu have not performed well in clinical trials. A team of scientists led by Richard Webby of St Jude Children’s Research Hospital, United States, investigated the reasons for this by comparing vaccine’s ability to stimulate the immune system in comparison to a vaccine to treat seasonal human flu. In contrast to previous hypotheses, Webby’s group found that only the avian H5N1 flu vaccine provoked a lesser release of neutralizing antibodies compared to the H7N9 (another avian flu) and seasonal flu vaccine, and hypothesized that differences in viral surface proteins may account for the difference. The authors hope this helps to direct future research into vaccine-induced immunity.

ACS Style

Sook-San Wong; Jennifer DeBeauchamp; Mark Zanin; Yilun Sun; Li Tang; Richard Webby. H5N1 influenza vaccine induces a less robust neutralizing antibody response than seasonal trivalent and H7N9 influenza vaccines. npj Vaccines 2017, 2, 1 -8.

AMA Style

Sook-San Wong, Jennifer DeBeauchamp, Mark Zanin, Yilun Sun, Li Tang, Richard Webby. H5N1 influenza vaccine induces a less robust neutralizing antibody response than seasonal trivalent and H7N9 influenza vaccines. npj Vaccines. 2017; 2 (1):1-8.

Chicago/Turabian Style

Sook-San Wong; Jennifer DeBeauchamp; Mark Zanin; Yilun Sun; Li Tang; Richard Webby. 2017. "H5N1 influenza vaccine induces a less robust neutralizing antibody response than seasonal trivalent and H7N9 influenza vaccines." npj Vaccines 2, no. 1: 1-8.

Journal article
Published: 17 March 2017 in Scientific Reports
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Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [GMT] < 10), low (GMT = 28.3), or high (GMT > 761.1) hemagglutination-inhibition (HAI) titers to the A/Viet Nam/1203/2004 (H5N1) virus. Ferrets were then challenged with the wild-type virus and disease severity and immunologic parameters were studied. The severity of infection and symptom profile were inversely associated with pre-challenge HAI titers in a dose-dependent manner. A vaccinated ferret with no detectable HAI-antibodies but high flu-specific IgG-antibody titers mounted rapid functional antibodies after infection and experienced milder disease compared to other ferrets in the group. Compared to naïve ferrets, all vaccinated ferrets showed improved cellular immunity in the lungs and peripheral blood. High number of IFNγ+ CD8- T cells in the airways was associated with early viral clearance. Thus, while neutralizing antibodies are the best correlate of protection, non-neutralizing antibodies can also be protective. This should be taken into consideration in future avian influenza vaccine trials.

ACS Style

Sook-San Wong; Susu Duan; Jennifer DeBeauchamp; Mark Zanin; Lisa Kercher; Stephanie Sonnberg; Thomas Fabrizio; Trushar Jeevan; Jeri-Carol Crumpton; Christine Oshansky; Yilun Sun; Li Tang; Paul G. Thomas; Richard Webby. The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants. Scientific Reports 2017, 7, 44727 .

AMA Style

Sook-San Wong, Susu Duan, Jennifer DeBeauchamp, Mark Zanin, Lisa Kercher, Stephanie Sonnberg, Thomas Fabrizio, Trushar Jeevan, Jeri-Carol Crumpton, Christine Oshansky, Yilun Sun, Li Tang, Paul G. Thomas, Richard Webby. The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants. Scientific Reports. 2017; 7 (1):44727.

Chicago/Turabian Style

Sook-San Wong; Susu Duan; Jennifer DeBeauchamp; Mark Zanin; Lisa Kercher; Stephanie Sonnberg; Thomas Fabrizio; Trushar Jeevan; Jeri-Carol Crumpton; Christine Oshansky; Yilun Sun; Li Tang; Paul G. Thomas; Richard Webby. 2017. "The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants." Scientific Reports 7, no. 1: 44727.

Journal article
Published: 01 February 2017 in Journal of Virology
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H7 subtype influenza A viruses are widely distributed and have been responsible for human infections and numerous outbreaks in poultry with significant impact. Despite this, the disease-causing potential of the precursor low-pathogenic (LP) H7 viruses from the wild bird reservoir has not been investigated. Our objective was to assess the disease-causing potential of 30 LP H7 viruses isolated from wild avian species in the United States and Canada using the DBA/2J mouse model. Without prior mammalian adaptation, the majority of viruses, 27 (90%), caused mortality in mice. Of these, 17 (56.7%) caused 100% mortality and 24 were of pathogenicity similar to that of A/Anhui/1/2013 (H7N9), which is highly pathogenic in mice. Viruses of duck origin were more pathogenic than those of shorebird origin, as 13 of 18 (72.2%) duck origin viruses caused 100% mortality while 4 of 12 (33.3%) shorebird origin viruses caused 100% mortality, despite there being no difference in mean lung viral titers between the groups. Replication beyond the respiratory tract was also evident, particularly in the heart and brain. Of the 16 viruses studied for fecal shedding, 11 were detected in fecal samples. These viruses exhibited a strong preference for avian-type α2,3-linked sialic acids; however, binding to mammalian-type α2,6-linked sialic acids was also detected. These findings indicate that LP avian H7 influenza A viruses are able to infect and cause disease in mammals without prior adaptation and therefore pose a potential public health risk. IMPORTANCE Low-pathogenic (LP) avian H7 influenza A viruses are widely distributed in the avian reservoir and are the precursors of numerous outbreaks of highly pathogenic avian influenza viruses in commercial poultry farms. However, unlike highly pathogenic H7 viruses, the disease-causing potential of LP H7 viruses from the wild bird reservoir has not been investigated. To address this, we studied 30 LP avian H7 viruses isolated from wild avian species in the United States and Canada using the DBA/2J mouse model. Surprisingly, the majority of these viruses, 90%, caused mortality in mice without prior mammalian adaptation, and 56.7% caused 100% mortality. There was also evidence of spread beyond the respiratory tract and fecal shedding. Therefore, the disease-causing potential of LP avian H7 influenza A viruses in mammals may be underestimated, and these viruses therefore pose a potential public health risk.

ACS Style

Mark Zanin; Zeynep A. Koçer; Rebecca L. Poulson; Jon D. Gabbard; Elizabeth W. Howerth; Cheryl A. Jones; Kimberly Friedman; Jon Seiler; Angela Danner; Lisa Kercher; Ryan McBride; James C. Paulson; David E. Wentworth; Scott Krauss; Stephen M. Tompkins; David E. Stallknecht; Robert G. Webster. Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model. Journal of Virology 2017, 91, 1 .

AMA Style

Mark Zanin, Zeynep A. Koçer, Rebecca L. Poulson, Jon D. Gabbard, Elizabeth W. Howerth, Cheryl A. Jones, Kimberly Friedman, Jon Seiler, Angela Danner, Lisa Kercher, Ryan McBride, James C. Paulson, David E. Wentworth, Scott Krauss, Stephen M. Tompkins, David E. Stallknecht, Robert G. Webster. Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model. Journal of Virology. 2017; 91 (3):1.

Chicago/Turabian Style

Mark Zanin; Zeynep A. Koçer; Rebecca L. Poulson; Jon D. Gabbard; Elizabeth W. Howerth; Cheryl A. Jones; Kimberly Friedman; Jon Seiler; Angela Danner; Lisa Kercher; Ryan McBride; James C. Paulson; David E. Wentworth; Scott Krauss; Stephen M. Tompkins; David E. Stallknecht; Robert G. Webster. 2017. "Potential for Low-Pathogenic Avian H7 Influenza A Viruses To Replicate and Cause Disease in a Mammalian Model." Journal of Virology 91, no. 3: 1.

Journal article
Published: 21 January 2017 in Journal of Ethnopharmacology
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Baphicacanthus cusia root also names “Nan Ban Lan Gen” has been traditionally used to prevent and treat influenza A virus infections. Here, we identified a peptide derivative, aurantiamide acetate (compound E17), as an active compound in extracts of B. cusia root. Although studies have shown that aurantiamide acetate possesses antioxidant and anti-inflammatory properties, the effects and mechanism by which it functions as an anti-viral or as an anti-inflammatory during influenza virus infection are poorly defined. Here we investigated the anti-viral activity and possible mechanism of compound E17 against influenza virus infection. The anti-viral activity of compound E17 against Influenza A virus (IAV) was determined using the cytopathic effect (CPE) inhibition assay. Viruses were titrated on Madin-Darby canine kidney (MDCK) cells by plaque assays. Ribonucleoprotein (RNP) luciferase reporter assay was further conducted to investigate the effect of compound E17 on the activity of the viral polymerase complex. HEK293T cells with a stably transfected NF-κB luciferase reporter plasmid were employed to examine the activity of compound E17 on NF-κB activation. Activation of the host signaling pathway induced by IAV infection in the absence or presence of compound E17 was assessed by western blotting. The effect of compound E17 on IAV-induced expression of pro-inflammatory cytokines was measured by real-time quantitative PCR and Luminex assays. Compound E17 exerted an inhibitory effect on IAV replication in MDCK cells but had no effect on avian IAV and influenza B virus. Treatment with compound E17 resulted in a reduction of RNP activity and virus titers. Compound E17 treatment inhibited the transcriptional activity of NF-κB in a NF-κB luciferase reporter stable HEK293 cell after stimulation with TNF-α. Furthermore, compound E17 blocked the activation of the NF-κB signaling pathway and decreased mRNA expression levels of pro-inflammatory genes in infected cells. Compound E17 also suppressed the production of IL-6, TNF-α, IL-8, IP-10 and RANTES from IAV-infected lung epithelial (A549) cells. These results indicate that compound E17 isolated from B. cusia root has potent anti-viral and anti-inflammatory effects on IAV-infected cells via inhibition of the NF-κB pathway. Therefore, compound E17 could be a potential therapeutic agent for the treatment of influenza.

ACS Style

Beixian Zhou; Zifeng Yang; Qitong Feng; Xiaoli Liang; Jing Li; Mark Zanin; Zhihong Jiang; Nanshan Zhong. Aurantiamide acetate from baphicacanthus cusia root exhibits anti-inflammatory and anti-viral effects via inhibition of the NF-κB signaling pathway in Influenza A virus-infected cells. Journal of Ethnopharmacology 2017, 199, 60 -67.

AMA Style

Beixian Zhou, Zifeng Yang, Qitong Feng, Xiaoli Liang, Jing Li, Mark Zanin, Zhihong Jiang, Nanshan Zhong. Aurantiamide acetate from baphicacanthus cusia root exhibits anti-inflammatory and anti-viral effects via inhibition of the NF-κB signaling pathway in Influenza A virus-infected cells. Journal of Ethnopharmacology. 2017; 199 ():60-67.

Chicago/Turabian Style

Beixian Zhou; Zifeng Yang; Qitong Feng; Xiaoli Liang; Jing Li; Mark Zanin; Zhihong Jiang; Nanshan Zhong. 2017. "Aurantiamide acetate from baphicacanthus cusia root exhibits anti-inflammatory and anti-viral effects via inhibition of the NF-κB signaling pathway in Influenza A virus-infected cells." Journal of Ethnopharmacology 199, no. : 60-67.

Journal article
Published: 15 January 2017 in Journal of Virology
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Neuraminidase (NA) is a sialidase expressed on the surface of influenza A viruses that releases progeny viruses from the surface of infected cells and prevents viruses becoming trapped in mucus. It is a homotetramer, with each monomer consisting of a transmembrane region, a stalk, and a globular head with sialidase activity. We recently characterized two swine viruses of the pandemic H1N1 lineage, A/swine/Virginia/1814-1/2012 (pH1N1 low -1) and A/swine/Virginia/1814-2/2012 (pH1N1 low -2), with almost undetectable NA enzymatic activity compared to that of the highly homologous A/swine/Pennsylvania/2436/2012 (pH1N1-1) and A/swine/Minnesota/2499/2012 (pH1N1-2) viruses. pH1N1-1 transmitted to aerosol contact ferrets, but pH1N1 low -1 did not. The aim of this study was to identify the molecular determinants associated with low NA activity as potential markers of aerosol transmission. We identified the shared unique substitutions M19V, A232V, D248N, and I436V (N1 numbering) in pH1N1 low -1 and pH1N1 low -2. pH1N1 low -1 also had the unique Y66D substitution in the stalk domain, where 66Y was highly conserved in N1 NAs. Restoration of 66Y was critical for the NA activity of pH1N1 low -1 NA, although 19M or 248D in conjunction with 66Y was required to recover the level of activity to that of pH1N1 viruses. Studies of NA stability and molecular modeling revealed that 66Y likely stabilized the NA homotetramer. Therefore, 66Y in the stalk domain of N1 NA was critical for the stability of the NA tetramer and, subsequently, for NA enzymatic activity. IMPORTANCE Neuraminidase (NA) is a sialidase that is one of the major surface glycoproteins of influenza A viruses and the target for the influenza drugs oseltamivir and zanamivir. NA is important as it releases progeny viruses from the surface of infected cells and prevents viruses becoming trapped in mucus. Mutations in the globular head domain that decrease enzymatic activity but confer resistance to NA inhibitors have been characterized; however, the importance of specific mutations in the stalk domain is unknown. We identified 66Y (N1 numbering), a highly conserved amino acid that was critical for the stability of the NA tetramer and, subsequently, for NA enzymatic activity.

ACS Style

Mark Zanin; Susu Duan; Sook-San Wong; Gyanendra Kumar; Pradyumna Baviskar; Emily Collin; Charles Russell; Subrata Barman; Benjamin Hause; Richard Webby. An Amino Acid in the Stalk Domain of N1 Neuraminidase Is Critical for Enzymatic Activity. Journal of Virology 2017, 91, e00868-16 .

AMA Style

Mark Zanin, Susu Duan, Sook-San Wong, Gyanendra Kumar, Pradyumna Baviskar, Emily Collin, Charles Russell, Subrata Barman, Benjamin Hause, Richard Webby. An Amino Acid in the Stalk Domain of N1 Neuraminidase Is Critical for Enzymatic Activity. Journal of Virology. 2017; 91 (2):e00868-16.

Chicago/Turabian Style

Mark Zanin; Susu Duan; Sook-San Wong; Gyanendra Kumar; Pradyumna Baviskar; Emily Collin; Charles Russell; Subrata Barman; Benjamin Hause; Richard Webby. 2017. "An Amino Acid in the Stalk Domain of N1 Neuraminidase Is Critical for Enzymatic Activity." Journal of Virology 91, no. 2: e00868-16.

Original article
Published: 23 September 2016 in Archives of Virology
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Nonstructural protein 1 (NS1) is a multifunctional protein that is a viral replication enhancer and virulence factor. In this study, we investigated the effect of the amino acid substitution G45R on the NS1 of A/Puerto Rico/8/1934 (H1N1) (G45R/NS1) on viral virulence and host gene expression in a mouse model and the human lung cell line A549. The G45R/NS1 virus had increased virulence by inducing an earlier and robust proinflammatory cytokine response in mice. Mice infected with the G45R/NS1 virus lost more body weight and had lower survival rates than mice infected with the wild type (WT/NS1) virus. Replication of the G45R/NS1 virus was higher than that of the WT/NS1 virus in vitro, but the replication of both viruses was similar in mouse lungs. In A549 cells, the majority of G45R/NS1 protein was localized in the cytoplasm whereas the majority of WT/NS1 protein was localized in the nucleus. Microarray analysis revealed that A549 cells infected with the G45R/NS1 virus had higher expression of genes encoding proteins associated with the innate immune response and cytokine activity than cells infected with the WT/NS1 virus. These data agree with cytokine production observed in mouse lungs. Our findings suggest that G45R on NS1 protein contributes to viral virulence by increasing the expression of inflammatory cytokines early in infection.

ACS Style

Challika Kaewborisuth; Bryan Kaplan; Mark Zanin; David Finkelstein; Richard J. Webby; Porntippa Lekcharoensuk. G45R on nonstructural protein 1 of influenza A virus contributes to virulence by increasing the expression of proinflammatory cytokines in mice. Archives of Virology 2016, 162, 45 -55.

AMA Style

Challika Kaewborisuth, Bryan Kaplan, Mark Zanin, David Finkelstein, Richard J. Webby, Porntippa Lekcharoensuk. G45R on nonstructural protein 1 of influenza A virus contributes to virulence by increasing the expression of proinflammatory cytokines in mice. Archives of Virology. 2016; 162 (1):45-55.

Chicago/Turabian Style

Challika Kaewborisuth; Bryan Kaplan; Mark Zanin; David Finkelstein; Richard J. Webby; Porntippa Lekcharoensuk. 2016. "G45R on nonstructural protein 1 of influenza A virus contributes to virulence by increasing the expression of proinflammatory cytokines in mice." Archives of Virology 162, no. 1: 45-55.

Journal article
Published: 12 July 2016 in Virology Journal
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The nonstructural protein 1 (NS1) of influenza A viruses can act as a viral replication enhancer by antagonizing type I interferon (IFN) induction and response in infected cells. We previously reported that A/Puerto Rico/8/1934 (H1N1) (PR8) containing the NS1 gene derived from A/swine/IA/15/1930 (H1N1) (IA30) replicated more efficiently than the wild type virus. Here, we identified amino acids in NS1 critical for enhancing viral replication. To identify a key amino acid in NS1 which can increase the virus replication, growth kinetics of PR8 viruses encoding single mutation in NS1 were compared in A549 cells. NS1 mutant functions were studied using dsRNA-protein pull down, RIG-I mediated IFNβ-promoter activity assays and growth curve analysis in murine lung epithelial type I (Let1) cells. The G45R mutation in the NS1 of PR8 (G45R/NS1) virus is critical for the enhanced viral replication in A549 cells. G45R/NS1 slightly decreased NS1 binding to dsRNA but did not interfere with its suppression of RIG-I-mediated type I IFN production. Likewise, replication of G45R/NS1 virus was increased in comparison to wild type virus in both wild type and type I interferon receptor null Let1 cells. The non-conserved amino acid, R45, enhances viral replication which is apparently independent of dsRNA binding and suppression of type I IFN, suggesting a non-characterized function of NS1 for the enhanced viral replication. As G45R/NS1 virus induced the type I IFN induction and response in infected A549 cells, it is also interesting to investigate virus virulence for further studies.

ACS Style

Challika Kaewborisuth; Mark Zanin; Hans Häcker; Richard J. Webby; Porntippa Lekcharoensuk. G45R mutation in the nonstructural protein 1 of A/Puerto Rico/8/1934 (H1N1) enhances viral replication independent of dsRNA-binding activity and type I interferon biology. Virology Journal 2016, 13, 127 .

AMA Style

Challika Kaewborisuth, Mark Zanin, Hans Häcker, Richard J. Webby, Porntippa Lekcharoensuk. G45R mutation in the nonstructural protein 1 of A/Puerto Rico/8/1934 (H1N1) enhances viral replication independent of dsRNA-binding activity and type I interferon biology. Virology Journal. 2016; 13 (1):127.

Chicago/Turabian Style

Challika Kaewborisuth; Mark Zanin; Hans Häcker; Richard J. Webby; Porntippa Lekcharoensuk. 2016. "G45R mutation in the nonstructural protein 1 of A/Puerto Rico/8/1934 (H1N1) enhances viral replication independent of dsRNA-binding activity and type I interferon biology." Virology Journal 13, no. 1: 127.

Review
Published: 01 February 2016 in Cell Host & Microbe
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The interaction between respiratory pathogens and their hosts is complex and incompletely understood. This is particularly true when pathogens encounter the mucus layer covering the respiratory tract. The mucus layer provides an essential first host barrier to inhaled pathogens that can prevent pathogen invasion and subsequent infection. Respiratory mucus has numerous functions and interactions, both with the host and with pathogens. This review summarizes the current understanding of respiratory mucus and its interactions with the respiratory pathogens Pseudomonas aeruginosa, respiratory syncytial virus and influenza viruses, with particular focus on influenza virus transmissibility and host-range specificity. Based on current findings we propose that respiratory mucus represents an understudied host-restriction factor for influenza virus.

ACS Style

Mark Zanin; Pradyumna Baviskar; Robert Webster; Richard Webby. The Interaction between Respiratory Pathogens and Mucus. Cell Host & Microbe 2016, 19, 159 -168.

AMA Style

Mark Zanin, Pradyumna Baviskar, Robert Webster, Richard Webby. The Interaction between Respiratory Pathogens and Mucus. Cell Host & Microbe. 2016; 19 (2):159-168.

Chicago/Turabian Style

Mark Zanin; Pradyumna Baviskar; Robert Webster; Richard Webby. 2016. "The Interaction between Respiratory Pathogens and Mucus." Cell Host & Microbe 19, no. 2: 159-168.

Comment
Published: 07 December 2015 in The Lancet Infectious Diseases
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ACS Style

Mark Zanin; Richard Webby. Live-attenuated H7N9 influenza vaccine is weak, yet strong. The Lancet Infectious Diseases 2015, 16, 266 -267.

AMA Style

Mark Zanin, Richard Webby. Live-attenuated H7N9 influenza vaccine is weak, yet strong. The Lancet Infectious Diseases. 2015; 16 (3):266-267.

Chicago/Turabian Style

Mark Zanin; Richard Webby. 2015. "Live-attenuated H7N9 influenza vaccine is weak, yet strong." The Lancet Infectious Diseases 16, no. 3: 266-267.