ABSTRACT
A series of 33 human-avian and human-mammalian influenza virus reassortant 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) human virus with 5 avian and 1 mammalian influenza virus strains. All of the reassortants possessing NA genes of the H1N1 human parent virus and HA gene of an avian or mammalian parent virus had high values of infectivity/HA activity ratio. Since this feature could result from a limited virion aggregation, several reassortants were analyzed by velocity sucrose gradient centrifugation. In all cases tested, the reassortants of H3N1, H4N1, H10N1 and H13N1 composition were shown to be aggregated, whereas the preparations of the parent H1N1 virus and the reassortants possessing both HA and NA genes from the avian parents were represented mostly by single virions. The aggregates were formed at 4 degrees C and dissociated at 37 degrees C. The dissociation was blocked by an inhibitor of neuraminidase activity (2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid). The dissociation was reversible since the virions reaggregated at 4 degrees C; however, treatment with bacterial neuraminidase led to an irreversible dissociation of the aggregates. The tendency of the reassortants to aggregate correlates with an increased infectivity/HA ratio. No regular decrease in the neuraminidase activity in the virions of reassortants as compared to the parent H1N1 virus was revealed. The most likely explanation of the observed phenomenon seems to be an inefficient removal of sialic acid residues from the avian virus hemagglutinin by the human virus N1 neuraminidase.
Subject(s)
Influenza A virus/genetics , Membrane Glycoproteins/genetics , Reassortant Viruses/genetics , Viral Proteins/genetics , Animals , Chick Embryo , Chickens , Ducks , Electrophoresis, Polyacrylamide Gel , Genes, Viral , Hemagglutination, Viral , Hemagglutinins, Viral/genetics , Humans , Influenza A virus/physiology , Neuraminidase/genetics , Neuraminidase/pharmacology , RNA, Viral/analysis , Reassortant Viruses/physiology , Recombination, Genetic/drug effects , Temperature , WhalesABSTRACT
Some biological properties and the genome composition of antigenic recombinants obtained by crossing of human and animal influenza viruses were studied. Analysis of the recombinants has shown that upon heating of virions in vitro thermostability of the haemagglutinin (HA) does not necessarily correlate with the properties of parent HA; apparently it depended not only on the properties of the HA itself, but also on the peculiarities of other virion proteins. All recombinants obtained by crossing of pathogenic and apathogenic for mice parents either had a reduced pathogenicity for mice or were apathogenic. In some instances, reduction or loss of pathogenicity was observed in recombinants which inherited only one gene from the apathogenic parent; however, the data obtained suggest that pathogenicity involves functions of a number of genes. Human and animal influenza virus strains under study proved to be capable of replication in human embryo tracheal and kidney organ cultures. The degree of reproduction of the recombinants was either lower or higher as compared to the parent strains.
