Enhanced Human Immunodeficiency Virus-1 Replication in CD4+ T Cells Derived From Individuals With Latent Mycobacterium tuberculosis Infection
- 1 October 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 222 (9), 1550-1560
- https://doi.org/10.1093/infdis/jiaa257
Abstract
Background. Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. however, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4(+) T cells to HIV-1 infection. Methods. Plasma and blood CD4(+) T cells isolated from HIV-negative individuals across the Mtb infection spectrum and nonMtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4(+) T cells were infected with HIV-1 in vitro and were monitored for viral replication. Results. We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4(+) T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-i replication correlated with higher percentages of CD4(+) T-EM and T-TD cells. Conclusions. Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4(+) T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.Keywords
Funding Information
- Providence/Boston CFAR (P30AI042853)
- BU Clinical HIV/AIDS Research Training Program (5T32AI052074-13)
- Boston University
- Clinical and Translational Science Institute
- Clinical Research Training Program (UL1 TR001430)
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01 AI138960, R01 AI097117, R01 AI122842, U19 AI111276)
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