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

Abstract

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.