INFLUENZA-A VIRUS REASSORTANTS WITH SURFACE GLYCOPROTEIN GENES OF THEAVIAN PARENT VIRUSES - EFFECTS OF HA AND NA GENE COMBINATIONS ON VIRUS AGGREGATION

A series of 33 human-avian and human-mammalian influenza virus reassor tant clones possessing either HA or both HA and NA genes of the avian or mammalian virus was obtained by crosses of A/USSR/90/77 (H1N1) huma n virus with 5 avian and 1 mammalian influenza virus strains. All of t he reassortants possessing NA genes of the H1N1 human parent virus and HA gene of an avian or mammalian parent virus had high values of infe ctivity/HA activity ratio. Since this feature could result from a limi ted virion aggregation, several reassortants were analyzed by velocity sucrose gradient centrifugation. In all cases tested, the reassortant s of H3N1, H4N1, H10N1 and H13N1 composition were shown to be aggregat ed, whereas the preparations of the parent H1N1 virus and the reassort ants possessing both HA and NA genes from the avian parents were repre sented mostly by single virions. The aggregates were formed at 4-degre es-C and dissociated at 37-degrees-C. The dissociation was blocked by an inhibitor of neuraminidase activity (2-deoxy-2,3-dehydro-N-acetyl-n euraminic acid). The dissociation was reversible since the virions rea ggregated at 4-degrees-C; however, treatment with bacterial neuraminid ase led to an irreversible dissociation of the aggregates. The tendenc y of the reassortants to aggregate correlates with an increased infect ivity/HA ratio. No regular decrease in the neuraminidase activity in t he virions of reassortants as compared to the parent H1N1 virus was re vealed. The most likely explanation of the observed phenomenon seems t o be an inefficient removal of sialic acid residues from the avian vir us hemagglutinin by the human virus N1 neuraminidase.