Infection of HIV-1 transgenic mice with Mycobacterium avium induces the expression of infectious virus selectively from a mac-1-positive host cell population

Infection of HIV-l-transgenic mice with Mycobacterium avium, a common oppor tunistic pathogen in AIDS patients, was shown to result in increased tissue expression of viral specific transcripts. Moreover, by coculturing splenoc ytes from the transgenic animals with human T cells it was possible to demo nstrate that the elevation in HIV-1 mRNA triggered by M, avium infection re flects increased production of infectious virions. Viral immune activation was also shown to correlate with a marked elevation of p24 in supernatants of ex vivo cultured tissues and, more importantly, in systemic increases in the HIV-1 protein in plasma. Interestingly, these tissue and systemic p24 responses were found to be differentially regulated. Thus, while in vitro p 24 production by cultured splenocytes increased concurrently with bacterial loads during the first 6 wk of infection, levels of the Ag in plasma actua lly decreased. In situ localization experiments together with FAGS analysis of HIV-l-expressing splenocytes indicated that virus production is restric ted largely to cells of the monocyte/macrophage lineage. Indeed, in vitro p 24 expression by cells from noninfected transgenic mice was up-regulated by polyclonal stimulation of macrophages but not T cells. Together these resu lts underscore the importance of the macrophage reservoir in persistent vir us expression and establish a convenient and relevant animal model for stud ying the factors responsible for immune activation of HIV-1 induced by myco bacterial as well as other common coinfections encountered by AIDS patients .