G-Protein-Coupled Receptor and Ion Channel Genes Used by Influenza Virus for Replication
| Autor: | Abhijeet Bakre, Jackelyn Murray, Kyle V. Todd, Nichole Orr-Burks, Ralph A. Tripp |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Small interfering RNA
Immunology Biology Virus Replication Microbiology Ion Channels Virus Madin Darby Canine Kidney Cells Receptors G-Protein-Coupled 03 medical and health sciences Dogs Influenza A Virus H1N1 Subtype 0302 clinical medicine RNA interference Virology Influenza Human Pandemic Animals Humans Gene virus-host interactions 030304 developmental biology 0303 health sciences Host Microbial Interactions Host (biology) food and beverages Virus-Cell Interactions Influenza B virus Drug repositioning Viral replication A549 Cells siRNA 030220 oncology & carcinogenesis Insect Science influenza |
| Zdroj: | Journal of Virology |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Influenza epidemics result in morbidity and mortality each year. Vaccines are the most effective preventive measure but require annual reformulation, since a mismatch of vaccine strains can result in vaccine failure. Influenza virus causes epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses. Influenza viruses require host genes to replicate. RNA interference (RNAi) screens can identify host genes coopted by influenza virus for replication. Targeting these proinfluenza genes can provide therapeutic strategies to reduce virus replication. Nineteen proinfluenza G-protein-coupled receptor (GPCR) and 13 proinfluenza ion channel genes were identified in human lung (A549) cells by use of small interfering RNAs (siRNAs). These proinfluenza genes were authenticated by testing influenza virus A/WSN/33-, A/CA/04/09-, and B/Yamagata/16/1988-infected A549 cells, resulting in the validation of 16 proinfluenza GPCR and 5 proinfluenza ion channel genes. These findings showed that several GPCR and ion channel genes are needed for the production of infectious influenza virus. These data provide potential targets for the development of host-directed therapeutic strategies to impede the influenza virus productive cycle so as to limit infection. IMPORTANCE Influenza epidemics result in morbidity and mortality each year. Vaccines are the most effective preventive measure but require annual reformulation, since a mismatch of vaccine strains can result in vaccine failure. Antiviral measures are desirable particularly when vaccines fail. In this study, we used RNAi screening to identify several GPCR and ion channel genes needed for influenza virus replication. Understanding the host genes usurped by influenza virus during viral replication can help identify host genes that can be targeted for drug repurposing or for the development of antiviral drugs. The targeting of host genes is refractory to drug resistance generated by viral mutations, as well as providing a platform for the development of broad-spectrum antiviral drugs. |
| Databáze: | OpenAIRE |
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