This page has only limited features, please log in for full access.

Unclaimed
Sunil K. Lal
School of Science, Monash University, Bandar Sunway, Selangor, Malaysia

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Journal article
Published: 09 August 2021 in Expert Review of Vaccines
Reads 0
Downloads 0

Vaccine development for the disease caused by the herpes simplex virus (HSV) has been challenging over the years and is always in dire need of novel approaches for prevention and cure. To date, the HSV disease remains incurable and challenging to prevent. The disease is extremely widespread due to its high infection rate, resulting in millions of infection cases worldwide. This review first explains the diverse forms of HSV-related disease presentations and reports past vaccine history for the disease. Next, this review examines current and novel HSV vaccine approaches being studied and tested for efficacy and safety as well as vaccines in clinical trial phases I to III. Modern approaches to vaccine design using bioinformatics are described. Lastly, we discuss measures to enhance new vaccine development pipelines for HSV. : Modernized approaches using in silico analysis and bioinformatics are emerging methods that exhibit potential for producing vaccines with enhanced targets and formulations. Although not yet fully established for HSV disease, we describe current studies using these approaches for HSV vaccine design to shed light on these methods. In addition, we provide up-to-date requirements of immunogenicity, adjuvant selection and routes of administration.

ACS Style

Vindya Nilakshi Wijesinghe; Isra Ahmad Farouk; Nur Zawanah Zabidi; Ashwini Puniyamurti; Wee Sim Choo; Sunil Kumar Lal. Current vaccine approaches and emerging strategies against herpes simplex virus (HSV). Expert Review of Vaccines 2021, 1 -20.

AMA Style

Vindya Nilakshi Wijesinghe, Isra Ahmad Farouk, Nur Zawanah Zabidi, Ashwini Puniyamurti, Wee Sim Choo, Sunil Kumar Lal. Current vaccine approaches and emerging strategies against herpes simplex virus (HSV). Expert Review of Vaccines. 2021; ():1-20.

Chicago/Turabian Style

Vindya Nilakshi Wijesinghe; Isra Ahmad Farouk; Nur Zawanah Zabidi; Ashwini Puniyamurti; Wee Sim Choo; Sunil Kumar Lal. 2021. "Current vaccine approaches and emerging strategies against herpes simplex virus (HSV)." Expert Review of Vaccines , no. : 1-20.

Review paper
Published: 01 June 2021 in Virus Genes
Reads 0
Downloads 0

The Coronavirus Disease 2019 (COVID-19), a pneumonic disease caused by the SARS Coronavirus 2 (SARS-CoV-2), is the 7th Coronavirus to have successfully infected and caused an outbreak in humans. Genome comparisons have shown that previous isolates, the SARS-related coronavirus (SARSr-CoV), including the SARS-CoV are closely related, yet different in disease manifestation. Several explanations were suggested for the undetermined origin of SARS-CoV-2, in particular, bats, avian and Malayan pangolins as reservoir hosts, owing to the high genetic similarity. The general morphology and structure of all these viral isolates overlap with analogous disease symptoms such as fever, dry cough, fatigue, dyspnoea and headache, very similar to the current SARS-CoV-2. Chest CT scans for SARS-CoV-2, SARS-CoV and MERS-CoV reveal pulmonary lesions, bilateral ground-glass opacities, and segmental consolidation in the lungs, a common pathological trait. With greatly overlapping similarities among the previous coronavirus, the SARS-CoV, it becomes interesting to observe marked differences in disease severity of the SARS-CoV-2 thereby imparting it the ability to rapidly transmit, exhibit greater stability, bypass innate host defences, and increasingly adapt to their new host thereby resulting in the current pandemic. The most recent B.1.1.7, B.1.351 and P.1 variants of SARS-CoV-2, highlight the fact that changes in amino acids in the Spike protein can contribute to enhanced infection and transmission efficiency. This review covers a comparative analysis of previous coronavirus outbreaks and highlights the differences and similarities among different coronaviruses, including the most recent isolates that have evolved to become easily transmissible with higher replication efficiency in humans.

ACS Style

Zheng Yao Low; Ashley Jia Wen Yip; Anshika Sharma; Sunil K. Lal. SARS coronavirus outbreaks past and present—a comparative analysis of SARS-CoV-2 and its predecessors. Virus Genes 2021, 57, 307 -317.

AMA Style

Zheng Yao Low, Ashley Jia Wen Yip, Anshika Sharma, Sunil K. Lal. SARS coronavirus outbreaks past and present—a comparative analysis of SARS-CoV-2 and its predecessors. Virus Genes. 2021; 57 (4):307-317.

Chicago/Turabian Style

Zheng Yao Low; Ashley Jia Wen Yip; Anshika Sharma; Sunil K. Lal. 2021. "SARS coronavirus outbreaks past and present—a comparative analysis of SARS-CoV-2 and its predecessors." Virus Genes 57, no. 4: 307-317.

Journal article
Published: 31 May 2021 in Microorganisms
Reads 0
Downloads 0

The ongoing COVID-19 pandemic is a clear and present threat to global public health. Research into how the causative SARS-CoV-2 virus together with its individual constituent genes and proteins interact with target host cells can facilitate the development of improved strategies to manage the acute and long-term complications of COVID-19. In this study, to better understand the biological roles of critical SARS-CoV-2 proteins, we determined and compared the host transcriptomic responses of the HL-CZ human pro-monocytic cell line upon transfection with key viral genes encoding the spike S1 subunit, S2 subunit, nucleocapsid protein (NP), NSP15 (endoribonuclease), and NSP16 (2′-O-ribose-methyltransferase). RNA sequencing followed by gene set enrichment analysis and other bioinformatics tools revealed that host genes associated with topologically incorrect protein, virus receptor activity, heat shock protein binding, endoplasmic reticulum stress, antigen processing and presentation were up-regulated in the presence of viral spike S1 expression. With spike S2 expression, pro-monocytic genes associated with the interferon-gamma-mediated signaling pathway, regulation of phosphatidylinositol 3-kinase activity, adipocytokine signaling pathway, and insulin signaling pathway were down-regulated, whereas those associated with cytokine-mediated signaling were up-regulated. The expression of NSP15 induced the up-regulation of genes associated with neutrophil degranulation, neutrophil-mediated immunity, oxidative phosphorylation, prion disease, and pathways of neurodegeneration. The expression of NSP16 resulted in the down-regulation of genes associated with S-adenosylmethionine-dependent methyltransferase activity. The expression of NP down-regulated genes associated with positive regulation of neurogenesis, nervous system development, and heart development. Taken together, the complex transcriptomic alterations arising from these viral-host gene interactions offer useful insights into host genes and their pathways that potentially contribute to SARS-CoV-2 pathogenesis.

ACS Style

Anshika Sharma; Joe Ong; Mun Loke; Eng Chua; Joseph Lee; Hyung Choi; Yee Tan; Sunil Lal; Vincent Chow. Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes. Microorganisms 2021, 9, 1193 .

AMA Style

Anshika Sharma, Joe Ong, Mun Loke, Eng Chua, Joseph Lee, Hyung Choi, Yee Tan, Sunil Lal, Vincent Chow. Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes. Microorganisms. 2021; 9 (6):1193.

Chicago/Turabian Style

Anshika Sharma; Joe Ong; Mun Loke; Eng Chua; Joseph Lee; Hyung Choi; Yee Tan; Sunil Lal; Vincent Chow. 2021. "Comparative Transcriptomic and Molecular Pathway Analyses of HL-CZ Human Pro-Monocytic Cells Expressing SARS-CoV-2 Spike S1, S2, NP, NSP15 and NSP16 Genes." Microorganisms 9, no. 6: 1193.

Journal article
Published: 21 April 2021 in Viruses
Reads 0
Downloads 0

To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoproteins as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein, binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found that CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (Carcinoembryonic cell adhesion molecule 6 or CEACAM6) as a glycoprotein receptor for Influenza A virus.

ACS Style

Shah Rahman; Mairaj Ansari; Pratibha Gaur; Imtiyaz Ahmad; Chandrani Chakravarty; Dileep Verma; Anshika Sharma; Sanjay Chhibber; Naila Nehal; Dagmar Wirth; Sunil Lal. The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus. Viruses 2021, 13, 726 .

AMA Style

Shah Rahman, Mairaj Ansari, Pratibha Gaur, Imtiyaz Ahmad, Chandrani Chakravarty, Dileep Verma, Anshika Sharma, Sanjay Chhibber, Naila Nehal, Dagmar Wirth, Sunil Lal. The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus. Viruses. 2021; 13 (5):726.

Chicago/Turabian Style

Shah Rahman; Mairaj Ansari; Pratibha Gaur; Imtiyaz Ahmad; Chandrani Chakravarty; Dileep Verma; Anshika Sharma; Sanjay Chhibber; Naila Nehal; Dagmar Wirth; Sunil Lal. 2021. "The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza A Virus." Viruses 13, no. 5: 726.

Review
Published: 29 January 2021 in Viruses
Reads 0
Downloads 0

Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naïve human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review.

ACS Style

Anshika Sharma; Isra Ahmad Farouk; Sunil Lal. COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention. Viruses 2021, 13, 202 .

AMA Style

Anshika Sharma, Isra Ahmad Farouk, Sunil Lal. COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention. Viruses. 2021; 13 (2):202.

Chicago/Turabian Style

Anshika Sharma; Isra Ahmad Farouk; Sunil Lal. 2021. "COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention." Viruses 13, no. 2: 202.

Microbiology
Published: 25 September 2020 in Frontiers in Microbiology
Reads 0
Downloads 0

Influenza A virus (IAV) poses a major threat to global public health and is known to employ various strategies to usurp the host machinery for survival. Due to its fast-evolving nature, IAVs tend to escape the effect of available drugs and vaccines thus, prompting the development of novel antiviral strategies. High-throughput mass spectrometric screen of host-IAV interacting partners revealed host Filamin A (FLNA), an actin-binding protein involved in regulating multiple signaling pathways, as an interaction partner of IAV nucleoprotein (NP). In this study, we found that the IAV NP interrupts host FLNA-TRAF2 interaction by interacting with FLNA thus, resulting in increased levels of free, displaced TRAF2 molecules available for TRAF2-ASK1 mediated JNK pathway activation, a pathway critical to maintaining efficient viral replication. In addition, siRNA-mediated FLNA silencing was found to promote IAV replication (87% increase) while FLNA-overexpression impaired IAV replication (65% decrease). IAV NP was observed to be a crucial viral factor required to attain FLNA mRNA and protein attenuation post-IAV infection for efficient viral replication. Our results reveal FLNA to be a host factor with antiviral potential hitherto unknown to be involved in the IAV replication cycle thus, opening new possibilities of FLNA-NP interaction as a candidate anti-influenza drug development target.

ACS Style

Anshika Sharma; Jyoti Batra; Olga Stuchlik; Matthew S. Reed; Jan Pohl; Vincent T. K. Chow; Suryaprakash Sambhara; Sunil K. Lal. Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein. Frontiers in Microbiology 2020, 11, 1 .

AMA Style

Anshika Sharma, Jyoti Batra, Olga Stuchlik, Matthew S. Reed, Jan Pohl, Vincent T. K. Chow, Suryaprakash Sambhara, Sunil K. Lal. Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein. Frontiers in Microbiology. 2020; 11 ():1.

Chicago/Turabian Style

Anshika Sharma; Jyoti Batra; Olga Stuchlik; Matthew S. Reed; Jan Pohl; Vincent T. K. Chow; Suryaprakash Sambhara; Sunil K. Lal. 2020. "Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein." Frontiers in Microbiology 11, no. : 1.

Review
Published: 22 September 2020 in Viruses
Reads 0
Downloads 0

Traditionally, drug discovery utilises a de novo design approach, which requires high cost and many years of drug development before it reaches the market. Novel drug development does not always account for orphan diseases, which have low demand and hence low-profit margins for drug developers. Recently, drug repositioning has gained recognition as an alternative approach that explores new avenues for pre-existing commercially approved or rejected drugs to treat diseases aside from the intended ones. Drug repositioning results in lower overall developmental expenses and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities. The greatest advantage of drug repositioning is that it breathes new life into the novel, rare, orphan, and resistant diseases, such as Cushing’s syndrome, HIV infection, and pandemic outbreaks such as COVID-19. Repositioning existing drugs such as Hydroxychloroquine, Remdesivir, Ivermectin and Baricitinib shows good potential for COVID-19 treatment. This can crucially aid in resolving outbreaks in urgent times of need. This review discusses the past success in drug repositioning, the current technological advancement in the field, drug repositioning for personalised medicine and the ongoing research on newly emerging drugs under consideration for the COVID-19 treatment.

ACS Style

Zheng Yao Low; Isra Ahmad Farouk; Sunil Kumar Lal. Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak. Viruses 2020, 12, 1058 .

AMA Style

Zheng Yao Low, Isra Ahmad Farouk, Sunil Kumar Lal. Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak. Viruses. 2020; 12 (9):1058.

Chicago/Turabian Style

Zheng Yao Low; Isra Ahmad Farouk; Sunil Kumar Lal. 2020. "Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak." Viruses 12, no. 9: 1058.

Editorial
Published: 09 August 2020 in Viruses
Reads 0
Downloads 0

We are in the midst of a pandemic where the infective agent has been identified, but how it causes mild disease in some and fatally severe disease in other infected

ACS Style

Sunil K. Lal. Influenza A Virus: Host–Virus Relationships. Viruses 2020, 12, 870 .

AMA Style

Sunil K. Lal. Influenza A Virus: Host–Virus Relationships. Viruses. 2020; 12 (8):870.

Chicago/Turabian Style

Sunil K. Lal. 2020. "Influenza A Virus: Host–Virus Relationships." Viruses 12, no. 8: 870.

Journal article
Published: 15 April 2020 in Viruses
Reads 0
Downloads 0

Micro RNAs (miRNAs) are a class of small non-coding single-stranded RNA, which play an important role in modulating host-Influenza A virus (IAV) crosstalk. The interplay between influenza and miRNA interaction is defined by a plethora of complex mechanisms, which are not fully understood yet. Here, we demonstrate that in IAV infected A549 cells, a synchronous increase was observed in the expression of mTOR up to 24 hpi and significant downregulation at 48 hpi. Additionally, NP of IAV interacts with mTOR and modulates the levels of mTOR mRNA and protein, thus regulating the translation of host cell. RNA sequencing and qPCR analysis of IAV-infected A549 cells and NP transfected cells revealed that miR-101 downregulates mTOR transcripts at later stages of infection. Ectopic expression of miR-101 mimic led to a decrease in expression of NP, a reduction in IAV titer and replication. Moreover, treatment of the cells with Everolimus, a potent inhibitor of mTOR, resulted in an increase of miR-101 transcript levels, which further suppressed the viral protein synthesis. Collectively, the data suggest a novel mechanism that IAV stimulates mTOR pathway at early stages of infection; however, at a later time-point, positive regulation of miR-101 restrains the mTOR expression, and hence, the viral propagation.

ACS Style

Shipra Sharma; Anirvan Chatterjee; Purnima Kumar; Sunil Lal; Kiran Kondabagil. Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway. Viruses 2020, 12, 444 .

AMA Style

Shipra Sharma, Anirvan Chatterjee, Purnima Kumar, Sunil Lal, Kiran Kondabagil. Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway. Viruses. 2020; 12 (4):444.

Chicago/Turabian Style

Shipra Sharma; Anirvan Chatterjee; Purnima Kumar; Sunil Lal; Kiran Kondabagil. 2020. "Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway." Viruses 12, no. 4: 444.

Review
Published: 13 April 2020 in Viruses
Reads 0
Downloads 0

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.

ACS Style

Kavitha Ganesan Nathan; Sunil K. Lal. The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication. Viruses 2020, 12, 436 .

AMA Style

Kavitha Ganesan Nathan, Sunil K. Lal. The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication. Viruses. 2020; 12 (4):436.

Chicago/Turabian Style

Kavitha Ganesan Nathan; Sunil K. Lal. 2020. "The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication." Viruses 12, no. 4: 436.

Original article
Published: 24 January 2020 in Letters in Applied Microbiology
Reads 0
Downloads 0

Neuraminidase (NA) is an integral membrane protein of Influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two‐hybrid screen and found acute myeloid leukemia marker 1 (AML1) as a novel interacting partner of IAV‐NA. The interaction was further validated by co‐immunoprecipitation in IAV infected cells and in an in‐vitro coupled‐transcription translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose dependent manner. As expected, we also observed an increase in the IFNβ levels, the first line of defense against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFNβ levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFNβ. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an anti‐viral response against influenza A virus infection.

ACS Style

Pratibha Gaur; Purnima Kumar; Abhinay Sharma; Sunil K Lal. AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN‐β response in infected mammalian cells. Letters in Applied Microbiology 2020, 70, 252 -258.

AMA Style

Pratibha Gaur, Purnima Kumar, Abhinay Sharma, Sunil K Lal. AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN‐β response in infected mammalian cells. Letters in Applied Microbiology. 2020; 70 (4):252-258.

Chicago/Turabian Style

Pratibha Gaur; Purnima Kumar; Abhinay Sharma; Sunil K Lal. 2020. "AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN‐β response in infected mammalian cells." Letters in Applied Microbiology 70, no. 4: 252-258.

Review
Published: 06 December 2019 in Reviews in Medical Virology
Reads 0
Downloads 0

Viruses are obligate parasites known to interact with a wide variety of host proteins at different stages of infection. Current antiviral treatments target viral proteins and may be compromised due to the emergence of drug resistant viral strains. Targeting viral‐host interactions is now gaining recognition as an alternative approach against viral infections. Recent research has revealed that heterogeneous ribonucleoprotein A1, an RNA‐binding protein, plays an essential functional and regulatory role in the life cycle of many viruses. In this review, we summarize the interactions between heterogeneous ribonucleoprotein A1 (hnRNPA1) and multiple viral proteins during the life cycle of RNA and DNA viruses. hnRNPA1 protein levels are modulated differently, in different viruses, which further dictates its stability, function, and intracellular localization. Multiple reports have emphasized that in Sindbis virus, enteroviruses, porcine endemic diarrhea virus, and rhinovirus infection, hnRNPA1 enhances viral replication and survival. However, in others like hepatitis C virus and human T‐cell lymphotropic virus, it exerts a protective response. The involvement of hnRNPA1 in viral infections highlights its importance as a central regulator of host and viral gene expression. Understanding the nature of these interactions will increase our understanding of specific viral infections and pathogenesis and eventually aid in the development of novel and robust antiviral intervention strategies.

ACS Style

RamanDeep Kaur; Sunil K. Lal. The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections. Reviews in Medical Virology 2019, 30, e2097 .

AMA Style

RamanDeep Kaur, Sunil K. Lal. The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections. Reviews in Medical Virology. 2019; 30 (2):e2097.

Chicago/Turabian Style

RamanDeep Kaur; Sunil K. Lal. 2019. "The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections." Reviews in Medical Virology 30, no. 2: e2097.

Review
Published: 31 January 2019 in Reviews in Medical Virology
Reads 0
Downloads 0

Tetherin, an interferon‐inducible gene was first discovered to be an antiviral factor in 2008. A vast range of viruses, such as influenza A virus (IAV), dengue virus, Ebola virus, HIV, and RSV, have been reported to be susceptible to the antiviral activity of tetherin. Multiple reports have been published encompassing the role of tetherin in the IAV life cycle. To date, nine reports have been published regarding the role of tetherin in the IAV life cycle, with four reports supporting tetherin as an antiviral factor while five other reports suggesting no effect. To this end, this review summarizes the list of viruses currently known to be inhibited by tetherin and describes mechanisms used by viruses to overcome the antiviral potential of tetherin. Further, using IAV as disease model, we provide existing evidence in favor and against tetherin being considered as an antiviral candidate. Subsequent analysis of the experimental procedures across IAV‐tetherin published reports revealed that the experimental setup (ie, cell lines, transfection reagents, and multiplicity of infection), strain‐specific activity of NS1, and differing roles of NS1 in different cell lines may add up to the contributing factors leading to the discrepancies observed.

ACS Style

Anshika Sharma; Sunil K. Lal. Is tetherin a true antiviral: The influenza a virus controversy. Reviews in Medical Virology 2019, 29, e2036 .

AMA Style

Anshika Sharma, Sunil K. Lal. Is tetherin a true antiviral: The influenza a virus controversy. Reviews in Medical Virology. 2019; 29 (3):e2036.

Chicago/Turabian Style

Anshika Sharma; Sunil K. Lal. 2019. "Is tetherin a true antiviral: The influenza a virus controversy." Reviews in Medical Virology 29, no. 3: e2036.

Journal article
Published: 18 November 2018 in Viruses
Reads 0
Downloads 0

Influenza still remains one of the most challenging diseases, posing a significant threat to public health. Host lipid rafts play a critical role in influenza A virus (IAV) assembly and budding, however, their role in polyvalent IAV host binding and endocytosis had remained elusive until now. In the present study, we observed co-localization of IAV with a lipid raft marker ganglioside, GM1, on the host surface. Further, we isolated the lipid raft micro-domains from IAV infected cells and detected IAV protein in the raft fraction. Finally, raft disruption using Methyl-β-Cyclodextrin revealed significant reduction in IAV host binding, suggesting utilization of host rafts for polyvalent binding on the host cell surface. In addition to this, cyclodextrin mediated inhibition of raft-dependent endocytosis showed significantly reduced IAV internalization. Interestingly, exposure of cells to cyclodextrin two hours post-IAV binding showed no such reduction in IAV entry, indicating use of raft-dependent endocytosis for host entry. In summary, this study demonstrates that host lipid rafts are selected by IAV as a host attachment factors for multivalent binding, and IAV utilizes these micro-domains to exploit raft-dependent endocytosis for host internalization, a virus entry route previously unknown for IAV.

ACS Style

Dileep Kumar Verma; Dinesh Gupta; Sunil Kumar Lal. Host Lipid Rafts Play a Major Role in Binding and Endocytosis of Influenza A Virus. Viruses 2018, 10, 650 .

AMA Style

Dileep Kumar Verma, Dinesh Gupta, Sunil Kumar Lal. Host Lipid Rafts Play a Major Role in Binding and Endocytosis of Influenza A Virus. Viruses. 2018; 10 (11):650.

Chicago/Turabian Style

Dileep Kumar Verma; Dinesh Gupta; Sunil Kumar Lal. 2018. "Host Lipid Rafts Play a Major Role in Binding and Endocytosis of Influenza A Virus." Viruses 10, no. 11: 650.

Research article
Published: 18 October 2018 in Journal of Cellular Biochemistry
Reads 0
Downloads 0

Neuraminidase protein (NA) of influenza A virus (IAV) is popularly known for its sialidase function to assist in the release of progeny virus. However, involvement of NA in other stages of the IAV life cycle also indicates its multifunctional nature and necessity to interact with other host proteins. Here, we report a host protein—heat shock protein 90 (Hsp90), as a novel interacting partner of IAV NA. A classical yeast two‐hybrid screen was conducted to identify a new host interacting partner for NA and the interaction was further validated by coimmunoprecipitation from cells, transiently expressing both proteins and also from IAV‐infected cells. Confocal imaging showed that both proteins colocalized in the cytoplasm in transfected host cells. Interestingly, increased levels of NA in the presence of Hsp90 was observed, which tends to decrease if adenosine triphosphatase activity of Hsp90 is inhibited using 17‐N‐allylamino‐17‐demethoxygeldanamycin (17AAG). This establishes viral NA as a client protein of host chaperone Hsp90 contributing toward NA's stability via the NA‐Hsp90 interaction. This is the first report showing the interaction of NA with Hsp90 and its role in stabilizing viral NA thus preventing it from degradation. Enhanced cell survival in the presence of this interaction was also observed, thus suggesting the requirement of stable viral NA, post‐IAV infection, for efficient virus production in infected mammalian cells.

ACS Style

Purnima Kumar; Pratibha Gaur; Rashmi Kumari; Sunil K Lal. Influenza A virus neuraminidase protein interacts with Hsp90, to stabilize itself and enhance cell survival. Journal of Cellular Biochemistry 2018, 120, 6449 -6458.

AMA Style

Purnima Kumar, Pratibha Gaur, Rashmi Kumari, Sunil K Lal. Influenza A virus neuraminidase protein interacts with Hsp90, to stabilize itself and enhance cell survival. Journal of Cellular Biochemistry. 2018; 120 (4):6449-6458.

Chicago/Turabian Style

Purnima Kumar; Pratibha Gaur; Rashmi Kumari; Sunil K Lal. 2018. "Influenza A virus neuraminidase protein interacts with Hsp90, to stabilize itself and enhance cell survival." Journal of Cellular Biochemistry 120, no. 4: 6449-6458.

Review
Published: 14 August 2018 in Frontiers in Microbiology
Reads 0
Downloads 0

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

ACS Style

Zhi Y. Kho; Sunil K. Lal. The Human Gut Microbiome – A Potential Controller of Wellness and Disease. Frontiers in Microbiology 2018, 9, 1835 .

AMA Style

Zhi Y. Kho, Sunil K. Lal. The Human Gut Microbiome – A Potential Controller of Wellness and Disease. Frontiers in Microbiology. 2018; 9 ():1835.

Chicago/Turabian Style

Zhi Y. Kho; Sunil K. Lal. 2018. "The Human Gut Microbiome – A Potential Controller of Wellness and Disease." Frontiers in Microbiology 9, no. : 1835.

Review article
Published: 03 February 2017 in Frontiers in Microbiology
Reads 0
Downloads 0

Multiple outbreaks of Zika virus (ZIKV), a mosquito-borne virus belonging to the Flaviviridae family, have been reported since its discovery in the 1940s. ZIKV infections have known to be primarily asymptomatic while causing mild illness in a few cases. However, the recent emergence and spread of ZIKV in the Americas has resulted in the declaration of “Public Health Emergency of International Concern” due to the potential association between the infection and prenatal microcephaly or other brain anomalies. In Brazil, a 20-fold increase in prenatal microcephaly cases and 19% increase in Guillain-Barré Syndrome (GBS) cases were reported in 2015, as compared to the preceding year. The probable deleterious effects of ZIKV infection prompt the urgent development of diagnostics and therapeutics. To this end, the existing evidences supporting the increasingly common prenatal microcephaly and GBS association and the current known ZIKV transmission dynamics, modes of detection (molecular and serology-based), and current control strategies are summarized in this review. This review also emphasizes the importance of understanding ZIKV transmission in order to design a sensitive yet cost and time-efficient detection technique. Development of an efficient detection technique would subsequently allow for better surveillance and control of ZIKV infection. Currently, limited literature is available on the pathogenesis of ZIKV, hence, focusing on the modes of ZIKV transmission could potentially contribute to the understanding of the disease spectrum and formulation of targeted treatment and control.

ACS Style

Anshika Sharma; Sunil K. Lal. Zika Virus: Transmission, Detection, Control, and Prevention. Frontiers in Microbiology 2017, 8, 110 .

AMA Style

Anshika Sharma, Sunil K. Lal. Zika Virus: Transmission, Detection, Control, and Prevention. Frontiers in Microbiology. 2017; 8 ():110.

Chicago/Turabian Style

Anshika Sharma; Sunil K. Lal. 2017. "Zika Virus: Transmission, Detection, Control, and Prevention." Frontiers in Microbiology 8, no. : 110.

Preprint
Published: 30 January 2017
Reads 0
Downloads 0

To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoprotein as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (CEACAM6) as a glycoprotein receptor for Influenza A virus.Significance StatementCells are enclosed by a semipermeable membrane that allows selective exchange of biomolecules between cells and their surroundings. A set of specialized proteins in this semipermeable membrane, work like gatekeepers to the cell and regulate entry of these biomolecules. One class of such surface proteins is termed as receptors. Viruses bind to one or more of these receptors and manipulate gatekeepers for their own successful entry into host-cells. A membrane protein that influenza A virus (Flu virus) uses for entry into the cells was not discovered till date. This study reports for the first time, a receptor for influenza A virus, that was sought after by researchers for decades. The viral receptor is a promising target that can be used to inhibit virus entry into host cells.

ACS Style

Shah Kamranur Rahman; Mairaj Ahmed Ansari; Pratibha Gaur; Imtiyaz Ahmad; Chandrani Chakravarty; Dileep Kumar Verma; Sanjay Chhibber; Naila Nehal; Shanmugaapriya Sellathanby; Dagmar Wirth; Gulam Waris; Sunil K. Lal. The immunomodulatory CEA cell adhesion molecule 6 (CEACAM6/CD66c) is a candidate receptor for the influenza A virus. 2017, 104026 .

AMA Style

Shah Kamranur Rahman, Mairaj Ahmed Ansari, Pratibha Gaur, Imtiyaz Ahmad, Chandrani Chakravarty, Dileep Kumar Verma, Sanjay Chhibber, Naila Nehal, Shanmugaapriya Sellathanby, Dagmar Wirth, Gulam Waris, Sunil K. Lal. The immunomodulatory CEA cell adhesion molecule 6 (CEACAM6/CD66c) is a candidate receptor for the influenza A virus. . 2017; ():104026.

Chicago/Turabian Style

Shah Kamranur Rahman; Mairaj Ahmed Ansari; Pratibha Gaur; Imtiyaz Ahmad; Chandrani Chakravarty; Dileep Kumar Verma; Sanjay Chhibber; Naila Nehal; Shanmugaapriya Sellathanby; Dagmar Wirth; Gulam Waris; Sunil K. Lal. 2017. "The immunomodulatory CEA cell adhesion molecule 6 (CEACAM6/CD66c) is a candidate receptor for the influenza A virus." , no. : 104026.

Original article
Published: 09 December 2016 in Archives of Virology
Reads 0
Downloads 0

The matrix protein 2 (M2) is a spliced product of segment 7 genome of influenza A virus. Previous studies indicate its role in uncoating of the viral ribonucleoprotein complex during viral entry and in membrane scission while budding. Despite its crucial role in the viral life cycle, little is known about its subcellular distribution and dynamics. In this study, we have shown that the M2 protein is translocated from the membrane to the cytoplasm by a retrograde route via endosomes and the Golgi network. It utilizes retromer cargo while moving from the endosome to the trans-Golgi network and prevents endosome fusion with the lysosome. Further, M2 interacts with the endoplasmic-reticulum-resident AAA-ATPase p97 for its release into the cytoplasm. Our study also revealed that the M2 protein in the cellular milieu does not undergo ubiquitin-mediated proteasomal degradation. The migration of M2 through this pathway inside the infected cell suggests possible new roles that the M2 protein may have in the host cytoplasm, apart from its previously described functions.

ACS Style

Sanchari Bhowmick; Chandrani Chakravarty; Shanmugaapriya Sellathamby; Sunil K. Lal. The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation. Archives of Virology 2016, 162, 919 -929.

AMA Style

Sanchari Bhowmick, Chandrani Chakravarty, Shanmugaapriya Sellathamby, Sunil K. Lal. The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation. Archives of Virology. 2016; 162 (4):919-929.

Chicago/Turabian Style

Sanchari Bhowmick; Chandrani Chakravarty; Shanmugaapriya Sellathamby; Sunil K. Lal. 2016. "The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation." Archives of Virology 162, no. 4: 919-929.

Journal article
Published: 11 January 2016 in Scientific Reports
Reads 0
Downloads 0

A unique feature of influenza A virus (IAV) life cycle is replication of the viral genome in the host cell nucleus. The nuclear import of IAV genome is an indispensable step in establishing virus infection. IAV nucleoprotein (NP) is known to mediate the nuclear import of viral genome via its nuclear localization signals. Here, we demonstrate that cellular heat shock protein 40 (Hsp40/DnaJB1) facilitates the nuclear import of incoming IAV viral ribonucleoproteins (vRNPs) and is important for efficient IAV replication. Hsp40 was found to interact with NP component of IAV RNPs during early stages of infection. This interaction is mediated by the J domain of Hsp40 and N-terminal region of NP. Drug or RNAi mediated inhibition of Hsp40 resulted in reduced nuclear import of IAV RNPs, diminished viral polymerase function and attenuates overall viral replication. Hsp40 was also found to be required for efficient association between NP and importin alpha, which is crucial for IAV RNP nuclear translocation. These studies demonstrate an important role for cellular chaperone Hsp40/DnaJB1 in influenza A virus life cycle by assisting nuclear trafficking of viral ribonucleoproteins.

ACS Style

Janendra K Batra; Shashank Tripathi; Amrita Kumar; Jacqueline M. Katz; Nancy J. Cox; Renu B. Lal; Suryaprakash Sambhara; Sunil K. Lal. Human Heat shock protein 40 (Hsp40/DnaJB1) promotes influenza A virus replication by assisting nuclear import of viral ribonucleoproteins. Scientific Reports 2016, 6, 19063 .

AMA Style

Janendra K Batra, Shashank Tripathi, Amrita Kumar, Jacqueline M. Katz, Nancy J. Cox, Renu B. Lal, Suryaprakash Sambhara, Sunil K. Lal. Human Heat shock protein 40 (Hsp40/DnaJB1) promotes influenza A virus replication by assisting nuclear import of viral ribonucleoproteins. Scientific Reports. 2016; 6 (1):19063.

Chicago/Turabian Style

Janendra K Batra; Shashank Tripathi; Amrita Kumar; Jacqueline M. Katz; Nancy J. Cox; Renu B. Lal; Suryaprakash Sambhara; Sunil K. Lal. 2016. "Human Heat shock protein 40 (Hsp40/DnaJB1) promotes influenza A virus replication by assisting nuclear import of viral ribonucleoproteins." Scientific Reports 6, no. 1: 19063.