A mouse hepatotropic variant of influenza virus

Abstract

A hepatotropic variant of avian influenza virus A/Turkey/England 63 (Hav 1, Nav 3) was selected by serial passages in mouse liver. Adaptation to this organ was established after 13 in vivo passages and was found to improve during further passages as shown by increasing rates of replication in livers of ICR mice. The mutant virus finally selected was stable and differed from the original virus mainly in lethality upon intraperitoneal injection in mice, in its ability to grow to high titers in livers of susceptible animals and in plaque morphology in chick embryo fibroblasts. No differences were detected in hemagglutination inhibition and neutralization by standard mouse antisera. Pathogenicity for the liver was independent of the route of inoculation, included other laboratory animals sensitive to influenza virus and could be inhibited by amantadine. Fatal hepatitis in 50 per cent of susceptible mice by the intraperitoneal route required from 10 to 20 EID50-. Pathological changes consisted of severe necrosis of liver parenchyma accompanied by release of F antigen into the serum and were apparently due to virus replication in hepatic cells as evidenced by immunofluorescence. The main implications of this animal model for studies on experimental hepatitis and on myxovirus-host interactions in an organ not usually associated with influenza are discussed.

Mouse neurotropic recombinants of influenza A viruses

“…1 the turkey England strain is the only highly virulent strain (see also ref. 6). There was a delayed death of a number of animals during the test period after infection with FPV.…”

Adaptive Mutations Resulting in Enhanced Polymerase Activity Contribute to High Virulence of Influenza A Virus in Mice

“…Moderately pathogenic FLUAV strains can be rendered more pathogenic by repeated passages in experimentally infected animals (2,13,16,49,55). During such adaptations, the evolving viruses frequently seem to acquire virulence-enhancing mutations in the polymerase genes.…”

Pathology of Influenza Hepatitis in Susceptible and Genetically Resistant Mice

“…Whether it did so in each cell type contributing in liver architecture is difficult to decide. Its particular affinity for the liver, and within it for the hepatocyte, was attested by its ability to induce liver cell necrosis even when in oculated by the intranasal or subcutaneous routes [Haller, 1975], In this sense it behaved like a true hepatitis virus.…”

“…Evidence that the lesions described were caused by focal virus infec tions rests on synchrony between viral replication in the liver and spread of lesions [Haller, 1975], on temporal coincidence (in susceptible ani mals) of death with overwhelming liver necrosis, on differential in severity of both clinical infection and histopathological changes between genetically susceptible and resistant animals, and on spatial coincidence of specific immunofluorescence with sites of necrosis and infiltration. Lesions were never seen in animals inoculated with normal allantoic fluid either intra peritoneally or intraportally.…”