Human immunodeficiency virus type 1 (HIV-1) quasispecies at the sites of Mycobacterium tuberculosis infection contribute to systemic HIV-1 heterogeneity.
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/microl, 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.
Collins
Kalonji R
KR
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Quiñones-Mateu
Miguel E
ME
Wu
Mianda
M
Luzze
Henry
H
Johnson
John L
JL
Hirsch
Christina
C
Toossi
Zahra
Z
Arts
Eric J
EJ
D017088:AIDS-Related Opportunistic Infections / Q000821:virology*; D000328:Adult; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015686:Gene Products, env / Q000235:genetics*; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis; D010802:Phylogeny; D010996:Pleural Effusion / Q000382:microbiology / Q000821:virology*; D017422:Sequence Analysis, DNA; D014396:Tuberculosis, Pleural / Q000382:microbiology / Q000821:virology*
D004279:DNA, Viral; D015686:Gene Products, env