Resistance To Retroviral Infection In Transgenic And Bone-Marrow Chimeric Mice Containing Fv4-Env-Expressing Hematopoietic-Cells

Mice and chickens that inherit certain retroviral envelope genes are resistant to infection with related retroviruses. Previously, we described two transgenic mouse strains bearing a retroviral envelope gene, Fv4 that confers resistance to infection with ecotropic retroviruses (T. I. Limjoco et al., 1993, 1. Virol 67, 4163-4168). Here, we present results with these and an additional transgenic strain that show that (1) the level of resistance is correlated with level of expression of the transgene, (2) low-level expression of the transgene is associated with an unexpected and possibly immune-mediated phenotype of recovery from viremia, (3) resistance can be transferred by bone marrow transplantation and is ''dominant'' in chimeras containing mixtures of transgenic resistant plus control bone marrow, and (4) transplantation after infection with Friend Virus is much less effective than transplantation before infection. We discuss the implications of these results for gene therapy of retroviral infection.