NEUTRALIZATION-RESISTANT VARIANTS OF INFECTIOUS HEMATOPOIETIC NECROSIS VIRUS HAVE ALTERED VIRULENCE AND TISSUE TROPISM

Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus that c auses an acute disease in salmon and trout. In this study, a correlati on between changes in tissue tropism and specific changes in the virus genome appeared to be made by examining four IHNV neutralization-resi stant variants (RB-1, RB-2, RB-3, and RB-4) that had been selected wit h the glycoprotein (G)-specific monoclonal antibody RB/B5. These varia nts were compared with the parental strain (RB-76) for their virulence and pathogenicity in rainbow trout after waterborne challenge. Varian ts RB-2, RB-3, and RB-4 were only slightly attenuated and showed distr ibutions of viral antigen in the livers and hematopoietic tissues of i nfected fish similar to those of the parental strain. Variant RB-1, ho wever, was highly attenuated and the tissue distribution of viral anti gen in RB-l-infected fish was markedly different, with more viral anti gen in brain tissue. The sequences of the G genes of all four variants and RB-76 were determined. No significant changes were found for the slightly attenuated variants, but RB-1 G had two changes at amino acid s 78 and 218 that dramatically altered its predicted secondary structu re. These changes are thought to be responsible for the altered tissue tropism of the virus. Thus, IHNV G, like that of rabies virus and ves icular stomatitis virus, plays an integral part in the pathogenesis of viral infection.