IN-VIVO EVOLUTION OF A NOVEL, SYNCYTIUM-INDUCING AND CYTOPATHIC FELINE LEUKEMIA-VIRUS VARIANT

Studies of feline leukemia virus (FeLV) have illustrated the importanc e of the genotype of the infecting virus in determining disease outcom e, In FeLV infections, as in other retroviral infections, it is less c lear hen; virus variants that evolve from the transmitted virus affect pathogenesis. We previously reported an analysis of the genotypic cha nges that occur in the viral envelope gene (env) in cats infected with a prototype transmissible FeLV clone, 61E (J, Rohn, M. Linenberger, E , Hoover, and J, Overbaugh, J, Virol, 68:2458-2467, 1994). In one cat, each variant (81T) had evolved, in addition to scattered amino acid c hanges, a four-amino-acid insertion with respect to 61E, This insertio n was located at the same site in the extracellular en,elope glycoprot ein,there the immunodeficiency-inducing molecular clone 61C possesses a sis-amino-acid insertion critical for its pathogenic phenotype, alth ough the sequences of the insertions were distinct, To determine wheth er acquisition of the four-amino-acid insertion was associated with a change in the replication or cytopathic properties of the virus, we co nstructed chimeras encoding 81T env genes in a 61E background, One rep resentative chimeric virus, EET(TE)-109, was highly cytopathic despite the fact that it replicated with delayed kinetics in the feline T-cel l line 3201 compared to the parental 61E virus, The phenotype of this virus was also no,el compared to other FeLVs, including both the paren tal virus 61E and the immunodeficiency-inducing variant 61C, because i nfection of T cells was associated with syncytium formation, Moreover, in single-cycle infection assays, the 81T-109 envelope demonstrated r eceptor usage properties distinct from those of both 61E and 61C envel ope, Thus, these studies demonstrate the evolution of a novel T-cell c ytopathic and syncytium-inducing FeLV in the host, The 81T virus will be valuable for dissecting the mechanism of T-cell killing by cytopath ic variants in the FeLV model.