Genetic relatedness of the nucleoprotein (NP) of recent swine, turkey, and human influenza A virus (H1N1) isolates.

The sequences of nucleoprotein (NP) genes of recent human and turkey isolates of influenza A viruses, which serologically could be correlated to contemporary swine viruses, were determined. These sequences were closely related to the NPs of these swine viruses and they formed a separate branch on the phylogenetic tree. While the early swine virus from 1931 resembled the avian strains in consensus amino acids of the NP and in its ability to rescue NP ts mutants of fowl plague virus in chicken embryo cells, the later strains on that branch were different: at 15 positions they have their own amino acids and they rescued the NP ts mutants only poorly. Of the NPs of the human New Jersey/76 isolates analysed, one clustered with the recent H1N1 swine viruses of the U.S.A., the other one with contemporary human strains. Since the NP is one of the main determinants of species specificity it is concluded that, although the H1N1 swine isolates from the U.S.A. form their own branch in the phylogenetic tree, they can be transmitted to humans and turkeys, but they do not spread further in these populations and so far have not contributed to human pandemics. It is not very likely that they will do so in future, since its branch in the phylogenetic tree develops further away from the human and avian branch.

Influenza A virus late mRNAs are specifically retained in the nucleus in the presence of a methyltransferase or a protein kinase inhibitor.

The synthesis of influenza A virus RNA and proteins represents a highly regulated process whereby variable amounts of early and late viral RNAs and proteins may be produced. This regulation is upset by the presence of the methyltransferase inhibitor 3-deazaadenosine (3DA-Ado) or the protein kinase inhibitor H7, resulting in complete or partial inhibition of synthesis of late proteins but normal production of early proteins. Although the total yield of viral mRNAs is somewhat reduced by treatment with 3DA-Ado, the mRNAs that are produced can still be translated in vitro. Both 3DA-Ado and H7 interfere specifically with the transport of the late viral mRNAs from the nucleus to the cytoplasm, but do not affect transport of early mRNA. From these results we conclude that during influenza virus replication, posttranscriptional regulation takes place on the level of mRNA transport. Since hemagglutinin mRNA migrates to the cytoplasm in the presence of 3DA-Ado plus cycloheximide, we assume that a viral protein is involved in the regulation mechanism.