The HIV-1 Transgenic Nude Rat: A model of Pneumocystis Pneumonia

HIV-infected individuals are at increased risk for acute and chronic airway disease though there is currently no evidence that the virus can infect lung epithelium. Pneumocystisis a protozoan opportunistic pathogen that usually causes interstitial pneumonitis in patients with HIV/AIDS.We previously described the HIV-1 transgenic rat which bears a gag-pol –deleted HIV-1 genome that developed immunologic pathologies. In the current experiments, we studied the role of functional T cells in the development of Pneumocystis carinii(Pc) infection. We developed the HIV-1 Tg nude rat model by backcrossing onto thenude background from an HIV-1 Tg rat. Prior studies has determined that the HIV-1 transgene in rats results in a dysfunctional alveolar epithelial barrier and the alveolar macrophages from these HIV-1–transgenic rats have decreased intracellular expression of the GM-CSFRb subunit and decreased bacterial phagocytic function. We then hypothesizedthat having the HIV transgene on a nude background which lacksfunctional T cells will render them completely vulnerable to Pc infection even more so than the wild type rat and/or the HIV-1 Tg rat. After its development, the HIV-1 Tg nude rats showing signs of lethargy, dyspnea, and a dramatic weight losson gross pathology revealed generalized multifocal whitish – grey lung lesions. On microscopic examination the alveoli were filled with “foamy” material and interstitial pneumonitis. Silver methenamine stain demonstrated protozoan cysts and PCR of lung tissues confirmed the presence of Pneumocystis carinii. These observations substantiate that the HIV-1 transgenic nude rat model can be used as an appropriate small animal model to study the pathogenesis of HIV associated respiratory disease in patients.