Research Article: Association of Influenza Virus Proteins with Membrane Rafts

Date Published: July 25, 2011

Publisher: Hindawi Publishing Corporation

Author(s): Michael Veit, Bastian Thaa.


Assembly and budding of influenza virus proceeds in the viral budozone, a domain in the plasma membrane with characteristics of cholesterol/sphingolipid-rich membrane rafts. The viral transmembrane glycoproteins hemagglutinin (HA) and neuraminidase (NA) are intrinsically targeted to these domains, while M2 is seemingly targeted to the edge of the budozone. Virus assembly is orchestrated by the matrix protein M1, binding to all viral components and the membrane. Budding progresses by protein- and lipid-mediated membrane bending and particle scission probably mediated by M2. Here, we summarize the experimental evidence for this model with emphasis on the raft-targeting features of HA, NA, and M2 and review the functional importance of raft domains for viral protein transport, assembly and budding, environmental stability, and membrane fusion.

Partial Text

Influenza virus assembly and budding is linked to (coalesced) membrane rafts in the apical plasma membrane. Generally, the spike glycoproteins HA and NA are assumed to be raft-associated, while M2 is believed to be intrinsically excluded from rafts. The peripheral membrane protein M1 is considered not to have membrane subdomain specificity. In the next paragraphs, we describe the experimental evidence that had led to this model.

It is assumed that rafts play a decisive role at several steps during virus replication and are hence vital for virus viability. These steps include intracellular transport of viral proteins (most notably HA) to the assembly site, assembly and budding of progeny virus particles at the plasma membrane, environmental stability of the virus particles, and fusion of viral and host cell endosomal membrane upon virus entry.

In summary, HA might pass through a functional “raft cycle” during replication of influenza virus. In the Golgi, HA associates with membrane rafts, which might form vesicles to facilitate transport of entrapped proteins to the apical membrane. At the plasma membrane, HA induces the formation of the viral budozone, a membrane nanodomain where assembly of viral components and exclusion of cellular proteins occur. Upon assembly of all virus components, HA might cause bending of the membrane and M2, which is supposedly attracted to the edge of the viral budozone, might mediate pinching off of virus particles. Budding of virus particles through rafts equips the particle with an appropriate lipid mixture that protects particles from environmental damage and, in the case of cholesterol, might promote membrane fusion upon virus entry. Thus, rafts are functionally indispensable for the replication cycle of influenza virus and hence perhaps a possible target for anti-influenza drugs to be developed.




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