Negative-sense RNA viruses: An underexplored platform for examining virus–host lipid interactions

Abstract

Viruses are pathogenic agents that can infect all varieties of organisms, including plants, animals, and humans. These microscopic particles are genetically simple as they encode a limited number of proteins that undertake a wide range of functions. While structurally distinct, viruses often share common characteristics that have evolved to aid in their infectious life cycles. A commonly underappreciated characteristic of many deadly viruses is a lipid envelope that surrounds their protein and genetic contents. Notably, the lipid envelope is formed from the host cell the virus infects. Lipid-enveloped viruses comprise a diverse range of pathogenic viruses, which often lead to high fatality rates and many lack effective therapeutics and/or vaccines. This perspective primarily focuses on the negative-sense RNA viruses from the order Mononegavirales, which obtain their lipid envelope from the host plasma membrane. Specifically, the perspective highlights the common themes of host cell lipid and membrane biology necessary for virus replication, assembly, and budding.

The SARS-CoV-2 nucleoprotein associates with anionic lipid membranes

“…The role of host lipids in membrane localization of N and N incorporation into virions or VLPs has been underexplored. Many lipid-enveloped viruses that assemble and bud from the plasma membranes of host cells utilize lipid-protein interactions with a viral matrix protein (Freed 2006, Dick, Datta et al 2015, Bobone, Hilsch et al 2017, Favard, Chojnacki et al 2019, Husby and Stahelin 2021, Motsa and Stahelin 2021, Norris, Husby et al 2022) to mediate formation of viral progeny. Thus, in this study we examined the ability of the SARS-CoV-2 N protein to interact with lipid membranes in vitro , in cells and in silico and we performed molecular dynamics simulations to quantify the specific N/lipid interactions.…”

Evaluación de la interacción de la proteína de matriz del virus sincitial respiratorio humano (VSRH) con la proteína nucleolar fibrilarina

“…Después de la replicación viral y la transcripción, los RNPs y las proteínas virales restantes deben reunirse en algunas áreas de la membrana celular para que pueda ocurrir el ensamblaje (Husby & Stahelin, 2021). Particularmente, el sitio en donde se lleva a cabo el ensamblaje del virión, así como el sitio para la liberación de partículas virales son dominios ricos en colesterol conocidos como balsas lipídicas (Chang et al, 2012).…”

“…Esta liberación se produce porque las concentraciones de glicoproteínas y complejos RNPs generan una curvatura en la membrana celular que hace que se cierre parte de la membrana y la libere en el medio extracelular. Es importante señalar que la gemación del VSRH no se ve afectada por la inhibición del complejo de clasificación endosomal requerido para el transporte de proteínas (ESCRT), por lo tanto, este proceso podría utilizar un proceso novedoso para la escisión de membrana (Husby & Stahelin, 2021).…”