The lack of an inherent membrane targeting signal is responsible for the failure of the matrix (M1) protein of influenza A virus to bud into virus-like particles.
The matrix protein (M1) of influenza A virus is generally viewed as a key orchestrator in the release of influenza virions from the plasma membrane during infection. In contrast to this model, recent studies have indicated that influenza virus requires expression of the envelope proteins for budding of intracellular M1 into virus particles. Here we explored the mechanisms that control M1 budding. Similarly to previous studies, we found that M1 by itself fails to form virus-like-particles (VLPs). We further demonstrated that M1, in the absence of other viral proteins, was preferentially targeted to the nucleus/perinuclear region rather than to the plasma membrane, where influenza virions bud. Remarkably, we showed that a 10-residue membrane targeting peptide from either the Fyn or Lck oncoprotein appended to M1 at the N terminus redirected M1 to the plasma membrane and allowed M1 particle budding without additional viral envelope proteins. To further identify a functional link between plasma membrane targeting and VLP formation, we took advantage of the fact that M1 can interact with M2, unless the cytoplasmic tail is absent. Notably, native M2 but not mutant M2 effectively targeted M1 to the plasma membrane and produced extracellular M1 VLPs. Our results suggest that influenza virus M1 may not possess an inherent membrane targeting signal. Thus, the lack of efficient plasma membrane targeting is responsible for the failure of M1 in budding. This study highlights the fact that interactions of M1 with viral envelope proteins are essential to direct M1 to the plasma membrane for influenza virus particle release.
Wang
Dan
D
Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA.
Harmon
Aaron
A
Jin
Jing
J
Francis
David H
DH
Christopher-Hennings
Jane
J
Nelson
Eric
E
Montelaro
Ronald C
RC
Li
Feng
F
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000821:virology*; D002467:Cell Nucleus / Q000737:chemistry / Q000821:virology; D002522:Chlorocebus aethiops; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D021382:Protein Sorting Signals; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D022701:Virosomes / Q000378:metabolism; D057074:Virus Release
C488936:M1 protein, Influenza A virus; D021382:Protein Sorting Signals; D014763:Viral Matrix Proteins; D022701:Virosomes