HIV TYPE-1 INFECTION OF THE COTTON RAT (SIGMODON FULVIVENTER AND S-HISPIDUS)

Cotton rats (Sigmodon hispidus and S. fulviventer) are susceptible to many viruses that infect humans (e.g., poliovirus, respiratory syncyti al virus, influenza virus, adenovirus, and parainfluenza virus) and ha ve been influential in developing therapeutic clinical intervention st rategies for many viral infections of man. This study set out to deter mine whether cotton rats are susceptible to infection with HIV type 1 (HIV-1), Results indicate that HIV-1 does infect the cotton rat and S, fulviventer is more susceptible than S. hispidus, The virus was passa ged from animal to animal for a total of three serial passages; but HI V replicated poorly in vivo, was only detectable as proviral DNA, and never exceeded one provirus per 1.8 x 10(5) cotton rat peripheral bloo d mononuclear cells. Infection induced a distinct and characteristic a nti-HIV antibody response that, in some animals, included neutralizing antibodies, recognized all of the major HIV-1 antigens and the antibo dies lasted out to 52 wk post-infection. Neonate S, fulviventer were n ot more susceptible to infection than adults. In vitro culture studies produced indirect evidence of viral replication by detection of viral gag gene RNA in reverse transcriptase-PCR assays on viral culture sup ernatants, Collectively, these results indicate that HIV-1 can replica te in a nontransgenic rodent and that this system may have potential a s an animal model for HIV-1 infection if viral replication rates can b e improved in vivo.