The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART.

HIV-1 viral replication is limited in patients given highly active anti-retroviral therapy (HAART); however, HIV-1 viral proteins are still present. We demonstrate that the developing HIV-1Tg rat, which expresses all of the HIV-1 viral genes except the gag-pol replication genes, maintains lower body weight compared with the F344 control rat. Although HIV-1Tg rats eat and drink less than the control animals, they are not anorexic and show no evidence of anhedonia. At 19 months (mo) of age, HIV-1Tg rats begin to show clinical signs of wasting that progress to death. Using real-time RT-PCR, we compared the expression of the HIV viral proteins Tat, gp120, nef, and vif, in the HIV-1Tg rats at 2-3 mo of age with those at 10-11 mo of age. RNA levels of viral protein in the spleens of younger rats were significantly greater than those in the older rats (P<0.01). Conversely, viral protein mRNA levels in the spinal cord, cerebellum, and striatum were significantly greater in the older rats than in the younger animals (P<0.01). In the prefrontal cortex, Tat and nef expression was significantly greater at 2-3 mo of age than at 10-11 mo of age (P<0.05). These findings indicate that there may be age-dependent differential expression of various HIV viral proteins, with a switch from peripheral immune organs to the CNS, even when the animals are still pre-symptomatic. Our study also demonstrates that this non-infectious rat can be a useful model simulating HIV-1 infected individuals that are on HAART. Copyright 2009. Published by Elsevier B.V.