HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization.Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.Individuals infected with the human immunodeficiency virus (HIV) are susceptible to both routine and opportunistic infections of the lung. Despite the advent of highly active anti-retroviral therapy (HAART), lung disease continues to be the leading cause of death [1,2]. Interestingly, although infections account for the apparent majority of these lung-related deaths, there is growing evidence that HIV also increases the risk of chronic airway diseases such as emphysema. For example, an analysis of the Veterans Aging Cohort Study showed that HIV-infected subjects were 50–60% more likely to develop chronic obstructive pulmonary disease (emphysema and/or chronic bronchitis) than HIV-negative subjects, and that HIV infection was an independent risk factor even after accounting for age, race/ethnicity, smoking histories, and substance abuse [3]. Other studies show similar results and several recent excellent reviews summarize the clinical data to date as well as some of the laboratory-based research that is beginning to explore possible mechanisms [4-6]. A common target in both acute lung injuries such as pneumonia and chronic lung diseases such as emphysema is alveolar epithelial damage.