Friend or Foe: The Role of the Cytoskeleton in Influenza A Virus Assembly

Abstract

Influenza A Virus (IAV) is a respiratory virus that causes seasonal outbreaks annually and pandemics occasionally. The main targets of the virus are epithelial cells in the respiratory tract. Like many other viruses, IAV employs the host cell's machinery to enter cells, synthesize new genomes and viral proteins, and assemble new virus particles. The cytoskeletal system is a major cellular machinery, which IAV exploits for its entry to and exit from the cell. However, in some cases, the cytoskeleton has a negative impact on efficient IAV growth. In this review, we highlight the role of cytoskeletal elements in cellular processes that are utilized by IAV in the host cell. We further provide an in-depth summary of the current literature on the roles the cytoskeleton plays in regulating specific steps during the assembly of progeny IAV particles.

Keywords: actin; cytoskeleton; influenza; microtubules; virus assembly.

Figure 1

Roles of the actin cytoskeleton and microtubules at different steps of IAV Assembly. IAV assembly is initiated at the plasma membrane after the arrival of three transmembrane proteins, HA, NA, and M2, and the cytoplasmic protein M1 through the cytoplasm. Clustering of these viral proteins drives assembly of the virus particle, which could have a spherical or filamentous morphology. vRNPs are transported across the cytoplasm on Rab11+ vesicles and are incorporated into the assembling virus particle. Whether the actin cytoskeleton and/or microtubules (MT) promote (pos) or suppress (neg) individual IAV assembly steps is depicted.

Figure 2

The role of the actin cytoskeleton in spherical IAV assembly in host cells. (A) Contrasting roles for the actin cytoskeleton in spherical IAV assembly in different cell types. In IAV-permissive cells, such as epithelial cell lines and a macrophage-like cell line, the actin cytoskeleton either promotes or has no effects on IAV particle production. In contrast, the actin cytoskeleton restricts HA-M2 association and spherical IAV assembly in primary human macrophages. (B) Proposed mechanisms by which actin restricts spherical IAV assembly in primary human macrophages. Microdomain segregation: F-actin partitions HA- and M2-enriched plasma membrane microdomains. Suppression of membrane curvature: F-actin restricts HA-mediated curvature induction at the plasma membrane, which is required for M2 recruitment to the assembling particle. Blocking of cytoplasmic components: F-actin restricts trafficking and incorporation of other curvature-inducing structural components, that is, M1 and vRNP, to virus assembly sites.