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Amino acids have been implicated with virus infection and replication. Here, we demonstrate the effects of two basic amino acids, arginine and lysine, and their ester derivatives on infection of two enveloped viruses, SARS-CoV-2, and influenza A virus. We found that lysine and its ester derivative can efficiently block infection of both viruses in vitro. Furthermore, the arginine ester derivative caused a significant boost in virus infection. Studies on their mechanism of action revealed that the compounds potentially disturb virus uncoating rather than virus attachment and endosomal acidification. Our findings suggest that lysine supplementation and the reduction of arginine-rich food intake can be considered as prophylactic and therapeutic regimens against these viruses while also providing a paradigm for the development of broad-spectrum antivirals.
Ivonne Melano; Li-Lan Kuo; Yan-Chung Lo; Po-Wei Sung; Ni Tien; Wen-Chi Su. Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection. Viruses 2021, 13, 1301 .
AMA StyleIvonne Melano, Li-Lan Kuo, Yan-Chung Lo, Po-Wei Sung, Ni Tien, Wen-Chi Su. Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection. Viruses. 2021; 13 (7):1301.
Chicago/Turabian StyleIvonne Melano; Li-Lan Kuo; Yan-Chung Lo; Po-Wei Sung; Ni Tien; Wen-Chi Su. 2021. "Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection." Viruses 13, no. 7: 1301.
Emerging evidence highlights the role of non-coding small RNAs in host-influenza interaction. We have identified a Y RNA-derived small RNA, miR-1975, which is upregulated upon influenza A virus infection in A549 cells. The aim of this study is to investigate whether miR-1975 serves as an indicator of clinical severity upon influenza infection. We investigate the abundance of miR-1975 in sera from clinical patients and its correlation with hypoxemia status. We quantified its amounts in sera from influenza virus-infected patients and healthy volunteers by means of stem-loop RT-PCR. Median values of miR-1975 were significantly higher in influenza virus-infected patients, especially in hypoxemic patients. miR-1975 levels at the acute stage of the disease were highly correlated with the fraction of inspired oxygen used by the patients and total ventilator days. Receiver operator characteristic curve analysis revealed that miR-1975 levels in combination with days of fever before presenting to hospital had significant predictive value for hypoxemia and respiratory failure for patients infected with influenza virus. Our results reveal that circulating miR-1975 has great potential to serve as a biomarker for predicting prognosis in patients infected with influenza virus.
Yuag-Meng Liu; Hui-Chen Chen; Yi-Chun Chen; Wen-Ya Yu; Meng-Yen Ho; Chia-Yin Ho; Michael M.C. Lai; Wen-Chi Su. miR-1975 serves as an indicator of clinical severity upon influenza infection. European Journal of Clinical Microbiology & Infectious Diseases 2020, 40, 141 -149.
AMA StyleYuag-Meng Liu, Hui-Chen Chen, Yi-Chun Chen, Wen-Ya Yu, Meng-Yen Ho, Chia-Yin Ho, Michael M.C. Lai, Wen-Chi Su. miR-1975 serves as an indicator of clinical severity upon influenza infection. European Journal of Clinical Microbiology & Infectious Diseases. 2020; 40 (1):141-149.
Chicago/Turabian StyleYuag-Meng Liu; Hui-Chen Chen; Yi-Chun Chen; Wen-Ya Yu; Meng-Yen Ho; Chia-Yin Ho; Michael M.C. Lai; Wen-Chi Su. 2020. "miR-1975 serves as an indicator of clinical severity upon influenza infection." European Journal of Clinical Microbiology & Infectious Diseases 40, no. 1: 141-149.
Zika virus (ZIKV) is an important human pathogen associated with severe neurological disorders. Ubiquitination of viral proteins has diverse roles in viral life cycle and pathogenesis. Here, we found that perturbation of ubiquitin-proteasome system significantly suppressed production of infectious viral particles. Moreover, we demonstrated that ZIKV precursor membrane (prM) protein underwent ubiquitination and proteasomal degradation. Furthermore, we showed that co-expression of E protein with ubiquitination-deficient prM-6 K/6R mutant protein did not affect translocation of viral proteins into endoplasmic reticulum and trans-Golgi networks. Intriguingly, the co-expression of E and prM-6 K/6R mutant proteins led to formation of relatively aggregated viral protein complexes and resulted in diminishing secretion of viral proteins as compared to wild-type prM. Collectively, these results suggest that ubiquitinated ZIKV prM protein contributes to the release of viral proteins and provide a new insight into the mechanism involved in ZIKV replication biology.
Peter Nambala; Wen-Ya Yu; Yan-Chung Lo; Cheng Wen Lin; Wen-Chi Su. Ubiquitination of Zika virus precursor membrane protein promotes the release of viral proteins. Virus Research 2020, 286, 198065 .
AMA StylePeter Nambala, Wen-Ya Yu, Yan-Chung Lo, Cheng Wen Lin, Wen-Chi Su. Ubiquitination of Zika virus precursor membrane protein promotes the release of viral proteins. Virus Research. 2020; 286 ():198065.
Chicago/Turabian StylePeter Nambala; Wen-Ya Yu; Yan-Chung Lo; Cheng Wen Lin; Wen-Chi Su. 2020. "Ubiquitination of Zika virus precursor membrane protein promotes the release of viral proteins." Virus Research 286, no. : 198065.
Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control. The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 106 TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon. The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV’s non-structural protein expression. Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity. Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates.
Chien-Yi Lu; Chen-Sheng Lin; Hsueh-Chou Lai; Ya-Wen Yu; Chih-Yi Liao; Wen-Chi Su; Bo-Han Ko; Young-Sheng Chang; Su-Hua Huang; Cheng-Wen Lin. The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles. Viruses 2019, 11, 1005 .
AMA StyleChien-Yi Lu, Chen-Sheng Lin, Hsueh-Chou Lai, Ya-Wen Yu, Chih-Yi Liao, Wen-Chi Su, Bo-Han Ko, Young-Sheng Chang, Su-Hua Huang, Cheng-Wen Lin. The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles. Viruses. 2019; 11 (11):1005.
Chicago/Turabian StyleChien-Yi Lu; Chen-Sheng Lin; Hsueh-Chou Lai; Ya-Wen Yu; Chih-Yi Liao; Wen-Chi Su; Bo-Han Ko; Young-Sheng Chang; Su-Hua Huang; Cheng-Wen Lin. 2019. "The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles." Viruses 11, no. 11: 1005.
Multiple interplays between viral and host factors are involved in influenza virus replication and pathogenesis. Several small RNAs have recently emerged as important regulators of host response to viral infections. The aim of this study was to characterize the functional role of hsa-miR-1975, a Y5 RNA-derived small RNA, in defending influenza virus and delineate the mechanisms. We performed high throughput sequencing of small RNAs in influenza virus-infected cells to identify up- or down- regulated small RNA species. The expression of the most abundant RNA species (hsa-miR-1975) was validated by stem-loop reverse transcription-polymerase chain reaction (RT-PCR). Antiviral effects of hsa-miR-1975 were confirmed by Western Blot, RT-PCR and plaque assay. In vitro perturbation of hsa-miR-1975 combined with exosomes isolation was used to elucidate the role and mechanism of hsa-miR-1975 in the context of antiviral immunity. Small RNA sequencing revealed that hsa-miR-1975 was the most up-regulated small RNA in influenza virus-infected cells. The amount of intracellular hsa-miR-1975 increased in the late stage of the influenza virus replication cycle. The increased hsa-miR-1975 was at least partially derived from degradation of Y5RNA as a result of cellular apoptosis. Unexpectedly, hsa-miR-1975 mimics inhibited influenza virus replication while hsa-miR-1975 sponges enhanced the virus replication. Moreover, hsa-miR-1975 was secreted in exosomes and taken up by the neighboring cells to induce interferon expression. Our findings unravel a critical role of Y-class small RNA in host’s defense against influenza virus infection and reveal its antiviral mechanism through exosome delivery. This may provide a new candidate for targeting influenza virus.
Yuag-Meng Liu; Chung-Hsin Tseng; Yi-Chun Chen; Wen-Ya Yu; Meng-Yen Ho; Chia-Yin Ho; Michael M. C. Lai; Wen-Chi Su. Exosome-delivered and Y RNA-derived small RNA suppresses influenza virus replication. Journal of Biomedical Science 2019, 26, 1 -14.
AMA StyleYuag-Meng Liu, Chung-Hsin Tseng, Yi-Chun Chen, Wen-Ya Yu, Meng-Yen Ho, Chia-Yin Ho, Michael M. C. Lai, Wen-Chi Su. Exosome-delivered and Y RNA-derived small RNA suppresses influenza virus replication. Journal of Biomedical Science. 2019; 26 (1):1-14.
Chicago/Turabian StyleYuag-Meng Liu; Chung-Hsin Tseng; Yi-Chun Chen; Wen-Ya Yu; Meng-Yen Ho; Chia-Yin Ho; Michael M. C. Lai; Wen-Chi Su. 2019. "Exosome-delivered and Y RNA-derived small RNA suppresses influenza virus replication." Journal of Biomedical Science 26, no. 1: 1-14.
Genome-wide RNA interference (RNAi) screening is an emerging and powerful technique for genetic screens, which can be divided into arrayed RNAi screen and pooled RNAi screen/selection based on different screening strategies. To date, several genome-wide RNAi screens have been successfully performed to identify host factors essential for influenza virus replication. However, the host factors identified by different research groups are not always consistent. Taking influenza virus screens as an example, we found that a number of screening parameters may directly or indirectly influence the primary hits identified by the screens. This review highlights the differences among the published genome-wide screening approaches and offers recommendations for performing a good pooled shRNA screen/selection.
Yu-Chi Chou; Michael Mc Lai; Yi-Chen Wu; Nai-Chi Hsu; King-Song Jeng; Wen-Chi Su. Variations in genome-wide RNAi screens: lessons from influenza research. Journal of Clinical Bioinformatics 2015, 5, 2 .
AMA StyleYu-Chi Chou, Michael Mc Lai, Yi-Chen Wu, Nai-Chi Hsu, King-Song Jeng, Wen-Chi Su. Variations in genome-wide RNAi screens: lessons from influenza research. Journal of Clinical Bioinformatics. 2015; 5 (1):2.
Chicago/Turabian StyleYu-Chi Chou; Michael Mc Lai; Yi-Chen Wu; Nai-Chi Hsu; King-Song Jeng; Wen-Chi Su. 2015. "Variations in genome-wide RNAi screens: lessons from influenza research." Journal of Clinical Bioinformatics 5, no. 1: 2.