hiv-1 replication is differentially regulated by distinct clinical strains of mycobacterium tuberculosishiv - 1复制不同受独特的结核分枝杆菌临床菌株.pdfVIP

HIV-1 Replication Is Differentially Regulated by Distinct Clinical Strains of Mycobacterium tuberculosis 1 2 1 3 3 1 Shahin Ranjbar *, Helena I. Boshoff , Amara Mulder , Noman Siddiqi , Eric J. Rubin , Anne E. Goldfeld * 1 Immune Disease Institute, Boston, Harvard Medical School, Boston, Massachusetts, United States of America, 2 The Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America, 3 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America Abstract Background: 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