HIV-1 Replication Is Differentially Regulated by Distinct Clinical Strains of Mycobacterium tuberculosisReportar como inadecuado

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Tuberculosis TB is the largest cause of death in human immunodeficiency virus type 1 HIV-1 infection, having claimed an estimated one third to one half of the 30 million AIDS deaths that have occurred worldwide. Different strains of Mycobacterium tuberculosis MTb, the causative agent of TB, are known to modify the host immune response in a strain-specific manner. However, a MTb strain-specific impact upon the regulation of HIV-1 replication has not previously been established.

Methology-Principal Findings

We isolated normal human peripheral blood mononuclear cells PBMC and co-infected them with HIV-1 and with either the well characterized CDC1551 or HN878 MTb clinical isolate. We show that HIV-1 co-infection with the CDC1551 MTb strain results in higher levels of virus replication relative to co-infection with the HN878 MTb strain ex vivo. Furthermore, we show that the distinct pattern of CDC1551 or HN878 induced HIV-1 replication is associated with significantly increased levels of TNF and IL-6, and of the transcription and nuclear translocation of the p65 subunit of the transcription factor NF-κB, by CDC1551 relative to HN878.


These results provide a precedent for TB strain-specific effects upon HIV-1 replication and thus for TB strain-specific pathogenesis in the outcome of HIV-1-TB co-infection. MTb strain-specific factors and mechanisms involved in the regulation of HIV-1 during co-infection will be of importance in understanding the basic pathogenesis of HIV-1-TB co-infection.

Autor: Shahin Ranjbar , Helena I. Boshoff, Amara Mulder, Noman Siddiqi, Eric J. Rubin, Anne E. Goldfeld



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