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The Replication of Type A Influenza Viruses in the Infant Rat: A Marker for Virus Attenuation

Department of Virology, Academic Division of Pathology, Medical School, University of Sheffield, Sheffield S10 2RX, U.K.

Twenty recombinant influenza virus strains bearing HSw1N1, H1N1 or H3N2 surface antigens, together with their respective wild-type or laboratory-propagated parent viruses, were inoculated into 2 day-old infant rats and their replication in the turbinates and lungs of these animals observed over a period of 5 days. In addition, the ability of each of the recombinant and parent viruses to enhance a subsequent infection of these infant rats by Haemophilus influenzae type b was determined. The results showed that both parent and recombinant viruses replicated less well in the lungs than in the turbinates of infant rats, but the titres in both tissues were generally lower for the recombinant strains. The capacity of the majority of the recombinant influenza viruses to promote bacterial infection of the infant rats, as determined by the incidence of H. influenzae bacteraemia and meningitis, was also markedly less than that of their parent viruses. A correlation between virulence for man and both the replication in infant rat turbinates and the ability to enhance H. influenzae infection, was established for the virus strains studied. The data are discussed in relationship to the value of the infant rat-H. influenzae system as a laboratory marker for the determination of the virulence of influenza virus strains.

^* Present Address: Department of Clinical Pathology, Yarmouk Hospital, Baghdad, Iraq.

Received 22 January 1980; accepted 10 March 1980.