Recombination of influenza A virus strains: effect on pathogenicity

Abstract

Influenza viruses can recombine genetic information, and progeny virus can be selected for desired genetic traits. A newly isolated strain can develop the ability to grow to higher titer in embryonated eggs by acquiring this trait from the AOPR8(HON1) strain, and can be selected by the terminal dilution technique and by treatment with anti-HON1 antisera. In addition to acquiring the ability to grow to high titer, surface antigens may also be transferred, and the progeny can be selected by immunologic methods. It appeared likely that other genes, including those coding for virulence or attenuation might also be exchanged during the recombination procedure. We explored this question by infecting mice with recent strains of H3N2 influenza virus, and with some of their progeny which had been selected for high virus yields from eggs, after recombination with the AOPR8(HON1) virus, a strain known to be virulent for mice. Influenza (H3N2) virus strains A/Scotland, A/Port Chalmers and A/England which were isolated and passaged in embryonated eggs did not cause death when administered intranasally to three-week-old Swiss mice; however, after recombination with the A/PR8(HON1) virus, these viruses become lethal in mice. This acquisition of virulence appears to be secondary to exchange of genetic information from the parent AOPR8 virus. Virus isolated from mice infected with these recombinants is antigenically H3N2, the mice develop anti-H3N2 antibodies.