Ht to be secondary to a defect in the hepatic cytochrome oxidase system [97]. This

Ht to be secondary to a defect in the hepatic cytochrome oxidase system [97]. This impairment could lead to an aberration in porphyrin metabolism and subsequently cause porphyria [97]. Predisposing factors for the development of PCT in HIV-1/AIDS patients are co-infection with hepatitis C, alcohol abuse and hepatotoxic drug consumption [93]. Major precautions have to be taken by caregivers of these individuals as HIV-1 virions have been isolated from blister fluid of PCT/HIV-1 patients [98]. Cutaneous drug reactions (CDRs) are often reported in AIDS patients as directly related to HIV-1 infection [99]. CDRs include a wide spectrum of disorders that range from mild morbilliform reactions ( 70 ) toDue to the high costs of non-human primate research, transgenic rodent models represent the best approach to reproduce pathologies seen in HIV-1 infection. In the late 1990s, a couple of rodent models seemed to be promising tools to study the pathogenesis of HIV-1associated complications. These models transgenically expressed the human marker, CD4 (hCD4), and the coreceptor, hCXCR4, or the chemokine receptor, hCCR5, respectively [106,107]. As promising as they could be, numerous drawbacks were observed in these mice, which included a lack of CD4+ T cells binding to HIV-1 protein gp120, and subsequent lack of infectivity and replication in the target cells [108]. From that experience, some AG-221 biological activity non-infectious transgenic murine models of HIV-1 with deleted gag and pol genes were created. These HIV-1 Tg mice developed pathologic conditions similar to their human counterparts with HIV-1 infection; including the development of skin disorders [109,110]. Such lesions were reported as proliferative epidermal lesions accompanied by progressive ulceration of the epidermis, or described as benign lesions resembling papillomas, Kaposi’s sarcoma-like lesions [14] or B cell lymphomas [111]. However, the data generated from these models evidenced several failures, including numerous post-entry blocks due to inefficient tat transactivation. The deficiency in Tat function was further correlated with its lack of interaction with a gene product encoded onCedeno-Laurent et al. Journal of the International AIDS Society 2011, 14:5 http://www.jiasociety.org/content/14/1/Page 8 ofhuman chromosome 12, named cyclin T [108]. Mice’s cyclin T does not interact functionally with tat, a fact that makes it a non-functional viral promoter [112] and consequently an unreliable model. In 2001, we developed an HIV-1 Tg rat that showed similar pathology to that expressed in HIV-1/AIDS patients, and that overcame some of the problems encountered in the Tg mouse [109]. Unlike mice carrying the same transgene, efficient viral gene expression occurred in lymph nodes, spleen, thymus and blood, suggesting a functional tat [109]. Additionally, the generation of an HIV-1 transgenic rat appears to be a much better model both from the standpoint of size and that rat-derived cells are permissive for post-entry steps in the HIV-1 replication cycle. As recently reported, the HIV-1 Tg rat developed skin lesions in about 30 of the littermates [10]. Histologically, these lesions exhibited epidermal hyperplasia and hyperkeratosis, with an intense lymphocytic infiltrate and epidermal necrosis. Additionally, while the Tg rat showed the same pattern of serum cytokines seen in HIV-1/AIDS patients with a shift from Th1 to Th2 cytokines [113], analysis of the lesional PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28388412 skin showed a mixed cytokine profile [10].