Infection of Rabbits with Human Immunodeficiency Virus I

Kindt, T

Abstract

Laboratory studies have continued on the rabbit model for HIV-1 infection. Studies in the current period were directed toward gaining information concerning endpoints that may be used to monitor infection of rabbits. This is a first step in designing experiments to test the effect of prophylactic and therapeutic strategies to block HIV-1 infection in the infected rabbit. Present data indicate that virus may be detected by PCR reaction in the spleen about 10 weeks following a single injection of HIV-1 infected A3.01 cells. When brains were studied from rabbits given the same single injection, virus was detected as early as seven weeks and after 10 weeks all rabbits were positive for HIV-1 sequences in the brain. Both DNA and RNA PCR techniques were used in this study. In addition, in situ hybridization has been used to detect viral RNA sequences in organs from rabbits given a single HIV-1 injection. The peripheral blood mononuclear cells (PBMC) from rabbits, however, are a poor source for viral isolation. Approximately 30 weeks post injection PBMC from a significant percentage of rabbits were HIV positive; before this only sporadic positive results were obtained. This period could be shortened by superinfection with HTLV-I. In this case the presence of virus could be detected as much as eight weeks earlier than in those rabbits given only the HIV-1 injection. In collaborative studies with a group at Oncogen, Inc., rabbit antisera with high known neutralizing HIV-1 titers have been used in passive immunization experiments. Antibody was administered to rabbits that were allotype matched to serum samples and samples taken in order to ascertain the titer on day of infection. These rabbits have been infected and organs are presently being monitored for presence of viral sequences. These studies should provide a means to distinguish between humoral and cellular factors involved in the protection against HIV-1 by the normal immune system.