Inflammatory papillomatous hyperplasia and epidermal necrosis in a transgenic rat for HIV-1.

Background: Skin lesions commonly affect AIDS patients. The pathogenesis of certain dermatologic disorders primarily associated to HIV-1 is unclear, and better forms of therapy for these conditions need to be discovered. Transgenic animal models represent a novel approach for the study of these disorders and for the quest of more effective forms of treatment.

Objective: Characterize this HIV-1 transgenic rat as a model to study skin diseases related to HIV/AIDS.

Methods: A transgenic rat was developed, using an HIV-1 construct with deleted gag and pol genes. Morphological and genotypical evaluations were followed by cytokine profile characterization of the lesions.

Results: We report the characterization of a colony of HIV-1 transgenic rats that developed skin lesions in a frequency of 22.5%. Cutaneous expression of functional HIV-1 transgenes correlated precisely with the severity of the phenotype. In early stages, rats manifested localized areas of xerosis and dispersed papulosquamous lesions. These hyperplastic manifestations were observed in conjunction with an increased epidermal expression of tat protein and a Th1/Th2 profile of cytokines. As the lesions progressed, they formed inflammatory plaques that subsequently ulcerated. Histologically, these lesions displayed a profound lymphocytic infiltrate, epidermal necrosis, and a marked increase of both Th1 and Th2 derived cytokines. Moreover, the presence of circulating IgG antibodies against HIV-1 gp120 was detected.

Conclusion: This animal model as other HIV-1 transgenic mice described in the past, is not able to fully explain the myriad of skin findings that can occur in HIV-infected humans; however, it represents a potential animal model system for the study of immune-mediated inflammatory skin diseases.