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Human Immunodeficiency Virus Type 1 (HIV-1)Quasispecies at the Sites of Mycobacterium tuberculosis InfectionContribute to Systemic HIV-1 Heterogeneity

2002; American Society for Microbiology; Volume: 76; Issue: 4 Linguagem: Inglês

10.1128/jvi.76.4.1697-1706.2002

1098-5514

Kalonji R. Collins, Miguel E. Quiñones‐Mateu, Mianda Wu, Henry Luzze, John L. Johnson, Christina S. Hirsch, Zahra Toossi, Eric J. Arts,

HIV/AIDS drug development and treatment

ABSTRACT We have recently reported an increased heterogeneity in the human immunodeficiency virus type 1 (HIV-1) envelope gene ( env ) in HIV-1-infected patients with pulmonary tuberculosis (TB) compared to patients with HIV-1 alone. This increase may be a result of dissemination of lung-derived HIV-1 isolates from sites of Mycobacterium tuberculosis infection and/or the systemic activation of the immune system in response to TB. To distinguish between these two mechanisms, blood and pleural fluid samples were obtained from HIV-1-infected patients with active pleural TB in Kampala, Uganda (CD4 cell counts of 34 to 705 cells/μl, HIV-1 plasma loads of 2,400 to 280,000 RNA copies/ml, and HIV-1 pleural loads of 7,600 to 4,500,000 RNA copies/ml). The C2-C3 coding region of HIV-1 env was PCR amplified from lysed peripheral blood mononuclear cells and pleural fluid mononuclear cells and reverse transcriptase-PCR amplified from plasma and pleural fluid HIV-1 virions of eight HIV-1 patients with pleural TB. Phylogenetic and phenetic analyses revealed a compartmentalization of HIV-1 quasispecies between blood and pleural space in four of eight patients, with migration events between the compartments. There was a trend for a greater genetic heterogeneity in the pleural space, which may be the result of an M. tuberculosis -mediated increase in HIV-1 replication and/or selection pressure at the site of infection. Collectively, these findings suggest that HIV-1 quasispecies in the M. tuberculosis -infected pleural space may leak into the systemic circulation and lead to increased systemic HIV-1 heterogeneity during TB.