The HIV-1 transgenic rat model of neuroHIV

Abstract

Despite the ability of current combination anti-retroviral therapy (cART) to limit the progression of HIV-1 to AIDS, HIV-positive individuals continue to experience neuroHIV in the form of HIV-associated neurological disorders (HAND), which can range from subtle to substantial neurocognitive impairment. NeuroHIV may also influence substance use, abuse, and dependence in HIV-positive individuals. Because of the nature of the virus, variables such as mental health co-morbidities make it difficult to study the interaction between HIV and substance abuse in human populations. Several rodent models have been developed in an attempt to study the transmission and pathogenesis of the HIV-1 virus. The HIV-1 transgenic (HIV-1Tg) rat is a reliable model of neuroHIV because it mimics the condition of HIV-infected patients on cART. Research using this model supports the hypothesis that the presence of HIV-1 viral proteins in the central nervous system increases the sensitivity and susceptibility of HIV-positive individuals to substance abuse.

Keywords: HIV-1 transgenic rat; NeuroHIV; Substance abuse.

Figure 1

Structural organization of the genes of the HIV-1 genome and provirus with functional deletion of gag and pol genes. The protein products encoded by the retroviral genes support the HIV-1 life cycle and contribute to the pathological conditions associated with HIV-1 infection. Although the functional deletion of the gag and pol genes renders the HIV-1Tg rat non-infectious, the production of the regulatory and accessory gene protein products results in neuroinflammation in the CNS (Royal, Wang et al. 2007; Rao, Kim et al. 2011; Homji, Mao et al. 2012; Royal 2012).