Inhibition of human immunodeficiency virus-1 (HIV-1) by beta-chemokine analogues in mononuclear cells from HIV-1-infected patients with active tuberculosis.
Tuberculosis (TB) enhances human immunodeficiency virus-1 (HIV-1) activity in patients with dual HIV-1/TB infection. Therapies that control augmentations of HIV-1 activity at sites of Mycobacterium tuberculosis (MTB) infection may be useful in inhibition of viral expansion. Regulated upon activation, normal T-cell expressed and secreted (RANTES) analogues (AOP and NNY) are potent in inhibiting the entry of primary HIV-1 isolates into host mononuclear cells. These analogues were used to inhibit MTB-induced HIV-1 entry in blood monunuclear cells (PBMC) from patients with pulmonary TB, and pleural fluid mononuclear cells (PFMC) from patients with pleural TB. PBMC or PFMC were cultured with and without MTB in presence and absence of RANTES analogues. HIV-1 strong stop DNA was assessed by real-time polymerase chain reaction (PCR) as a measure of infection. CCR5 mRNA was assessed by real-time reverse transcription (RT)-PCR and by immunostaining and FACS analysis. HIV-1 infection was induced by MTB in vitro in PBMC from the majority (14 of 20) of HIV-1/TB subjects, and new infection was inhibited by AOP- or NNY-RANTES. HIV-1 infection was also inhibited by these reagents in MTB-induced PFMC from three of three patients with pleural TB. Expression of CCR5 mRNA was significantly induced by MTB in PBMC from patients with pulmonary TB. Further, expression of CCR5 was higher in PFMC compared to PBMC from patients with pleural TB. Also, CCR5 was fourfold higher on CD14(+) pleural mononuclear cells than on CD4(+) lymphocytes. Blocking new HIV-1 infection of mononuclear cells may be useful in control of HIV-1 during dual HIV-1/TB infection.
Toossi
Z
Z
Case Western Reserve University, Cleveland, OH 44106, USA. zxt2@po.cwru.edu
Mayanja-Kizza
H
H
Baseke
J
J
Peters
P
P
Wu
M
M
Abraha
A
A
Aung
H
H
Okwera
A
A
Hirsch
C
C
Arts
E
E
D000328:Adult; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000031:analogs & derivatives / Q000494:pharmacology*; D019742:Chemokines, CC / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*; D014396:Tuberculosis, Pleural / Q000150:complications / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology
D018946:Chemokine CCL5; D019742:Chemokines, CC; D004279:DNA, Viral; D012333:RNA, Messenger; D019713:Receptors, CCR5; C111989:aminooxypentane-RANTES