Influenza Virus M2 Ion Channel Protein Is Necessary for Filamentous Virion Formation

Abstract

Influenza A virus buds from cells as spherical (ϳ100-nm diameter) and filamentous (ϳ100 nm ؋ 2 to 20 m) virions. Previous work has determined that the matrix protein (M1) confers the ability of the virus to form filaments; however, additional work has suggested that the influenza virus M2 integral membrane protein also plays a role in viral filament formation. In examining the role of the M2 protein in filament formation, we observed that the cytoplasmic tail of M2 contains several sites that are essential for filament formation. Additionally, whereas M2 is a nonraft protein, expression of other viral proteins in the context of influenza virus infection leads to the colocalization of M2 with sites of virus budding and lipid raft domains. We found that an amphipathic helix located within the M2 cytoplasmic tail is able to bind cholesterol, and we speculate that M2 cholesterol binding is essential for both filament formation and the stability of existing viral filaments.

Influenza C Virus: Structure and Function of M Gene and Its Products

“…Recently, the M2 proton-selective ion channel function mediates virus budding (Rossman et al, 2010b;. The M2 cytoplasmic tail also plays a role in progeny virus production and virion morphology (Chen et al, 2008;Iwatsuki-Horimoto et al 2006;McCown & Pekosz, 2005;Rossman et al, 2010a;Zhang et al, 2000). The influenza B virus BM2 protein has a proton channel activity (Mould et al, 2003), and is involved in the incorporation of the virus genome into virions (Imai et al, 2004;2008).…”

Discovery of Novel Antiviral Agents Directed Against the Influenza A Virus Nucleoprotein

“…www.intechopen.com binds to cholesterol and this allows M2 to alter membrane curvature at the site of virus budding (Rossman et al, 2010a(Rossman et al, , 2010b. Bud formation and bud release are the last steps of the viral life cycle.…”

Early host response and immune signaling to 2009 pandemic influenza A (H1N1) viruses in primary cell culture models.

“…The NP encapsidated vRNAs and the polymerase proteins form the viral ribonucleoprotein (vRNP) complex ( Figure 1A). IAVs are primarily spherical viruses but some filamentous forms have been reported [39].…”

“…The filamentous phenotype has been mapped to specific genomic segments and genotypic differences in amino acid sequences within HA, NA, M1, and M2 [39][40][41][42][43][44].The functions of each of the viral proteins are summarized in Table 1. The viral morphology will be described in further detail in the section on the life cycle.…”

“…Using a reverse genetics approach, the filamentous phenotype has been mapped to amino acids within HA, NA, M1, and M2 [39][40][41][42][43][44]. Changes in influenza HA and NA have result in irregularly shaped virions possibly as a result of clustering of HA and NA on lipid rafts prior to viral budding causing membrane deformation; however, these mechanisms remain unclear [44,215].…”