Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication in the lung.

Abstract

We investigated the in vivo effect of coinfection of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) replication using bronchoalveolar lavage (BAL) of 11 HIV-1-infected patients with pulmonary tuberculosis and 10 patients with no lung disease. Lung segments involved with pulmonary tuberculosis had significantly elevated HIV-1 branched DNA (bDNA) levels and p24 in BAL compared with lung segments uninvolved with tuberculosis or with BAL from patients with no lung disease. The BAL viral burden was higher than plasma HIV-1 in tuberculosis patients, indicating local production of virus. BAL HIV-1 bDNA declined over the course of treatment for tuberculosis in three patients who underwent serial bronchoscopies. Tumor necrosis factor-alpha (TNF-alpha) and HIV-1 bDNA particles were strongly correlated (r2 = 0.9, p < 0.01) in lung segments involved with tuberculosis. The deduced amino acid sequence of HIV-1 gp120 V3 region from involved segments of three patients with pulmonary tuberculosis showed basic substitutions associated with altered viral phenotype. Phylogenetic analysis of V3 sequences demonstrated that BAL HIV-1 RNA had diverged from plasma. These data support the conclusion that pulmonary tuberculosis enhances local HIV-1 replication in vivo.

Differentiation of Monocytes to Macrophages Switches theMycobacterium tuberculosisEffect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein β Expression

“…Macrophages in lung segments involved with tuberculosis lose C/EBP␤ expression, express another C/EBP site-binding activity, and support high level HIV-1 replication (4,5,15). As expected, PMA-treated THP-1 cells or primary macrophages infected in vitro with M. tuberculosis exhibited a type I IFN response characteristic of resting alveolar macrophages, which strongly expressed the inhibitory C/EBP␤ and suppressed HIV-1 replication (15).…”

“…Fewer than 3 in 10 5 alveolar macrophages are infected, even in advanced AIDS (3). Opportunistic infections such as pulmonary tuberculosis markedly up-regulate HIV-1 replication in the lung and lead to mutations in the viral envelope gp120 V3 region associated with increased virulence (4).…”

Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages

“…This may be due to increased HIV-1 replication and mutation in the lung produced by TB (3,4). Understanding the mechanisms underlying the synergistic interaction between HIV and TB may lead to improved strategies for the control of both infections (5).…”

Consequence on Treatment of TB Patients Affected by HIV/AIDS A Conceptual Research

“…TB and HIV also interact in the lungs, the site of primary infection with M. tuberculosis. In a recently published study of HIVinfected patients with TB, researchers found that the viral load was higher in the bronchoalveolar lavage fluid from the affected versus the unaffected lung and was correlated with levels of tumor necrosis factor in bronchoalveolar fluid [21] . Researchers used V3 loop viral sequences to construct a phylogenetic tree and observed that the HIV quasispecies from the affected lung differed from those in the plasma within the same patient.…”