SERINC5 restricts influenza virus infectivity

• Published in: PLoS pathogens Vol. 18; no. 10; p. e1010907
• Main Authors: Zhao, Fei, Xu, Fengwen, Liu, Xiaoman, Hu, Yamei, Wei, Liang, Fan, Zhangling, Wang, Liming, Huang, Yu, Mei, Shan, Guo, Li, Yang, Long, Cen, Shan, Wang, Jianwei, Liang, Chen, Guo, Fei
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 12.10.2022; Public Library of Science (PLoS)
• Subjects: Amino acids; Anemia; Antiviral drugs; Biology and life sciences; Cell fusion; Cell membranes; Cloning; Computer and Information Sciences; Control; Distribution; Equine infectious anemia; Glycoproteins; Glycosylation; Health aspects; Hemagglutinins; HIV; Human immunodeficiency virus; Infections; Infectivity; Influenza; Influenza A; Influenza viruses; Leukemia; Medicine and health sciences; Membrane fusion; Membrane proteins; Protein expression; Proteins; Research and Analysis Methods; Sensitivity analysis; Stomatitis; Viral diseases; Viruses; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1010907

SERINC5 is a multi-span transmembrane protein that is incorporated into HIV-1 particles in producing cells and inhibits HIV-1 entry. Multiple retroviruses like HIV-1, equine infectious anemia virus and murine leukemia virus are subject to SERINC5 inhibition, while HIV-1 pseudotyped with envelope glycoproteins of vesicular stomatitis virus and Ebola virus are resistant to SERINC5. The antiviral spectrum and the underlying mechanisms of SERINC5 restriction are not completely understood. Here we show that SERINC5 inhibits influenza A virus infection by targeting virus-cell membrane fusion at an early step of infection. Further results show that different influenza hemagglutinin (HA) subtypes exhibit diverse sensitivities to SERINC5 restriction. Analysis of the amino acid sequences of influenza HA1 strains indicates that HA glycosylation sites correlate with the sensitivity of influenza HA to SERINC5, and the inhibitory effect of SERINC5 was lost when certain HA glycosylation sites were mutated. Our study not only expands the antiviral spectrum of SERINC5, but also reveals the role of viral envelope glycosylation in resisting SERINC5 restriction.