Influenza A Virus: Cellular Entry
- PMID: 38159235
- DOI: 10.1007/978-3-031-40086-5_14
Influenza A Virus: Cellular Entry
Abstract
The frequent emergence of pathogenic viruses with pandemic potential has posed a significant threat to human health and economy, despite enormous advances in our understanding of infection mechanisms and devising countermeasures through developing various prophylactic and therapeutic strategies. The recent coronavirus disease (COVID-19) pandemic has re-emphasised the importance of rigorous research on virus infection mechanisms and highlighted the need for our preparedness for potential pandemics. Although viruses cannot self-replicate, they tap into host cell factors and processes for their entry, propagation and dissemination. Upon entering the host cells, viruses ingeniously utilise the innate biological functions of the host cell to replicate themselves and maintain their existence in the hosts. Influenza A virus (IAV), which has a negative-sense, single-stranded RNA as its genome, is no exception. IAVs are enveloped viruses with a lipid bilayer derived from the host cell membrane and have a surface covered with the spike glycoprotein haemagglutinin (HA) and neuraminidase (NA). Viral genome is surrounded by an M1 shell, forming a "capsid" in the virus particle. IAV particles use HA to recognise sialic acids on the cell surface of lung epithelial cells for their attachment. After attachment to the cell surface, IAV particles are endocytosed and sorted into the early endosomes. Subsequently, as the early endosomes mature into late endosomes, the endosomal lumen becomes acidified, and the low pH of the late endosomes induces conformational reaggangements in the HA to initiate fusion between the endosomal and viral membranes. Upon fusion, the viral capsid disintegrates and the viral ribonucleoprotein (vRNP) complexes containing the viral genome are released into the cytosol. The process of viral capsid disintegration is called "uncoating". After successful uncoating, the vRNPs are imported into the nucleus by importin α/β (IMP α/β), where viral replication and transcription take place and the new vRNPs are assembled. Recently, we have biochemically elucidated the molecular mechanisms of the processes of viral capsid uncoating subsequent viral genome dissociation. In this chapter, we present the molecular details of the viral uncoating process.
Keywords: HDAC6; In Vitro uncoating; Influenza A virus; TNPO1; Ubiquitin.
© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.
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References
-
- Alvarado-Facundo E, Gao Y, Ribas-Aparicio RM, Jimenez-Alberto A, Weiss CD, Wang W (2015) Influenza virus M2 protein ion channel activity helps to maintain pandemic 2009 H1N1 virus hemagglutinin fusion competence during transport to the cell surface. J Virol 89(4):1975–1985. https://doi.org/10.1128/JVI.03253-14 - DOI - PubMed
-
- Banerjee I, Miyake Y, Nobs SP, Schneider C, Horvath P, Kopf M, Matthias P, Helenius A, Yamauchi Y (2014) Influenza A virus uses the aggresome processing machinery for host cell entry. Science 346(6208):473–477. https://doi.org/10.1126/science.1257037 - DOI - PubMed
-
- Carlson CR, Asfaha JB, Ghent CM, Howard CJ, Hartooni N, Safari M, Frankel AD, Morgan DO (2020) Phosphoregulation of phase separation by the SARS-CoV-2 N protein suggests a biophysical basis for its dual functions. Mol Cell 80(6):1092–1103. e1094. https://doi.org/10.1016/j.molcel.2020.11.025 - DOI - PubMed - PMC
-
- Chavrier P, Parton RG, Hauri HP, Simons K, Zerial M (1990) Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell 62(2):317–329. https://doi.org/10.1016/0092-8674(90)90369-p - DOI - PubMed
-
- Chlanda P, Mekhedov E, Waters H, Schwartz CL, Fischer ER, Ryham RJ, Cohen FS, Blank PS, Zimmerberg J (2016) The hemifusion structure induced by influenza virus haemagglutinin is determined by physical properties of the target membranes. Nat Microbiol 1(6):16050. https://doi.org/10.1038/nmicrobiol.2016.50 - DOI - PubMed - PMC
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