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

Peng, Jinsong; Vigorito, Michael; Liu, Xiangqian; Zhou, Dunjing; Wu, Xiongwen; Chang, Sulie L.

doi:10.1016/j.jneuroim.2009.09.014

« Previous Next »Journal of Neuroimmunology
Volume 218, Issue 1 , Pages 94-101, 25 January 2010

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

Jinsong Peng
- TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, People's Republic of China
- Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey, USA
- Wuhan Centers for Disease Control and Prevention, Wuhan, People's Republic of China
Michael Vigorito
- Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey, USA
- Department of Psychology, Seton Hall University, South Orange, New Jersey, USA
Xiangqian Liu
- Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey, USA
Dunjing Zhou
- Wuhan Centers for Disease Control and Prevention, Wuhan, People's Republic of China
Xiongwen Wu
- TongJi Medical College, HuaZhong University of Science and Technology, Wuhan, People's Republic of China
Sulie L. Chang
- Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey, USA
- Department of Biological Sciences, Seton Hall University, South Orange, New Jersey, USA
- Corresponding author. Institute of NeuroImmune Pharmacology, Seton Hall University, McNulty Hall, Room 309, South Orange, NJ 07079, USA. Tel.: +1 973 761 9456; fax: +1 973 275 2489.

Received 1 August 2009; received in revised form 24 September 2009; accepted 24 September 2009. published online 16 November 2009.

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 19months (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 2–3mo of age with those at 10–11mo 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 2–3mo of age than at 10–11mo 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.