Influence of the host cell on influenza virus replication

The replication of influenza virus is characterized by a unique dependence upon host cell nuclear function. In contrast to all other negative strand RNA viruses, transcription from host cellular DNA is a prerequisite for the synthesis of virus-specific messenger RNA; new DNA synthesis is not required. We have analysed the distribution of each of the nine virus-specified proteins between the nucleus and cytoplasm of virus-infected cells, and find that in addition of the NP and the NS1 proteins, two of the three P proteins show preferential migration into the nucleus. This subgroup of virus proteins may be involved in the early transcription of the viral genome which probably occurs in the nucleus. In non-permissive cell lines and in cells whose DNA function has been impaired by treatment with ultraviolet light, N-acetoxyacetaminofluorene or low doses of actinomycin D, production of some late virus proteins is inhibited. The specific host function required for this switch to late protein synthesis is unknown but in the cells treated with actinomycin D an abnormal accumulation of virus-specific mRNA occurs in the nucleus. In all cases studied, synthesis of new vRNA ceases when production of these late proteins has been blocked.