EFFECT OF M1 PROTEIN AND LOW PH ON NUCLEAR TRANSPORT OF INFLUENZA-VIRUS RIBONUCLEOPROTEINS

Influenza virus enters its host cell by receptor-mediated endocytosis followed by acid-activated membrane fusion in endosomes. The viral rib onucleoprotein particles (vRNPs) delivered into the cytosol then disso ciate from the matrix protein, M1, and from each other, after which th ey are individually imported into the nucleus via the nuclear pores, F or some time, it has been believed that the low pH in endosomes may, i n some way, trigger the capsid disassembly events necessary for nuclea r transport, This report provides direct evidence that the association of M1 with vRNPs is sensitive to mildly acidic pH within the infected cell. Recombinant M1, expressed in cultured cells, was found to assoc iate with vRNPs and inhibit their nuclear import, Brief acidification of the cytosolic compartment eliminated the interfering activity and a llowed the incoming vRNPs to enter the nucleus, Newly assembled progen y M1-vRNP complexes in the cytosol of infected cells were also dissoci ated by brief acidification, Acidic pH was thus found to serve as a sw itch that allowed M1 to early out its multiple functions in the uncoat ing, nuclear transport, and assembly of vRNPs.