IL-8 decreases HIV-1 transcription in peripheral blood lymphocytes and ectocervical tissue explants.
IL-8 is enhanced in the peripheral blood and lymphoid tissue of HIV-infected individuals, suggesting that IL-8 is important in the pathogenesis of HIV-1 infection and progression to AIDS. Characterizing the mechanisms of IL-8 regulation of HIV-1 replication may be relevant in addressing the role of IL-8 as a therapeutic target in HIV-1 infection. We evaluated replication of primary R5-tropic HIV-1 in peripheral blood lymphocytes and ectocervical tissue explants infected in vitro in the presence of physiological concentrations of IL-8 found in the serum and genital tract secretions of HIV-infected individuals. To identify the specific stages of the viral life cycle targeted by IL-8, we performed real-time polymerase chain reaction to detect HIV-1 reverse transcription, integration, and transcription. Early during the infection, IL-8 decreased HIV-1 reverse transcription and viral integration. This effect was transient, as on day 4 after infection, we detected no differences on HIV-1 DNA or proviral DNA in peripheral blood lymphocyte. IL-8 decreased HIV-1 transcription in both lymphocytes and ectocervical tissue explants. The decrease in viral RNA expression was associated with reduced HIV-1 replication, as measured by viral p24 release in the culture supernatants. This is the first report to suggest that IL-8 decreases replication of primary R5-tropic HIV-1 by transcriptional mechanisms.
Rollenhagen
Christiane
C
V. A. Medical Center, White River Junction, VT 05009, USA.
Asin
Susana N
SN
D001769:Blood / Q000821:virology*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000821:virology*; D005260:Female; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology*; D008214:Lymphocytes / Q000821:virology*; D009924:Organ Culture Techniques; D048348:Reverse Transcription; D014158:Transcription, Genetic; D014779:Virus Replication
D016655:HIV Core Protein p24; D016209:Interleukin-8