Document Type
Journal Article
Publication Date
2017
Journal
PLoS ONE
Volume
12
Issue
9
DOI
10.1371/journal.pone.0185162
Abstract
Following proviral integration into the host cell genome and establishment of a latent state, the human immunodeficiency virus type 1 (HIV-1) can reenter a productive life cycle in response to various stimuli. HIV-1 reactivation occurs when transcription factors, such as nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFAT), and activator protein -1 (AP-1), bind cognate sites within the long terminal repeat (LTR) region of the HIV-1 provirus to promote transcription. Interestingly, pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) can reactivate latent HIV-1 through activation of the transcription factor NF-κB. Some PRRs are expressed on central memory CD4+ T cells (TCM), which in HIV-1 patients constitute the main reservoir of latent HIV-1. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), interacts with PRRs through membrane components. However, the ability of Mtb to reactivate latent HIV-1 has not been extensively studied. Here we show that phosphatidylinositol mannoside 6 (PIM6), a component of the Mtb membrane, in addition to whole bacteria in co-culture, can reactivate HIV-1 in a primary TCM cell model of latency. Using a JLAT model of HIV-1 latency, we found this interaction to be mediated through Toll-like receptor-2 (TLR-2). Thus, we describe a mechanism by which Mtb can exacerbate HIV-1 infection. We hypothesize that chronic Mtb infection can drive HIV-1 reactivation. The phenomenon described here could explain, in part, the poor prognosis that characterizes HIV-1/Mtb co-infection.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Larson, E., Novis, C., Martins, L., Macedo, A., Kimball, K., Bosque, A., Planelles, V., & Barrows, L. (2017). Mycobacterium tuberculosis reactivates latent HIV-1 in T cells in vitro. PLoS ONE, 12 (9). http://dx.doi.org/10.1371/journal.pone.0185162
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of PLoS ONE.