The influenza virus nucleoprotein (NP), matrix protein (M1), and ribon
ucleoproteins (vRNPs) undergo regulated nuclear import and export duri
ng infection, Their trafficking was analyzed by using interspecies het
erokaryons containing nuclei from infected and uninfected cells, Under
normal conditions, it was demonstrated that the vRNPs which were asse
mbled in the nucleus and transported to the cytosol were prevented fro
m reimport into the nucleus, To be import competent, they must first a
ssemble into virions and enter by the endosomal entry pathway, In infl
uenza virus mutant ts51, in which M1 is defective, direct reimport too
k place but was inhibited by heterologous expression of wild-type M1.
These data confirm Mi's role as the inhibitor of premature nuclear imp
ort and as the main regulator of nuclear transport of vRNPs, In additi
on to this vRNP shuttling, M1 also shuttled between the nucleus and th
e cytoplasm in ts51-infected cells. When NP was expressed in the absen
ce of virus infection, it was also found to be a shuttling protein.