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Bhat, K.H. and Chaitanya, C.K. and Parveen, N. and Varman, R. and Ghosh, S. and Mukhopadhyay, Sangita (2012) Proline-Proline-Glutamic Acid (PPE) Protein Rv1168c of Mycobacterium tuberculosis Augments Transcription from HIV-1 Long Terminal Repeat Promoter. Journal of Biological Chemistry, 287 (20). pp. 16930-16946. ISSN 0021-9258

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Abstract

Cells of the monocyte/macrophage lineage are shown to play a role in the pathogenesis of human immunodeficiency virus (HIV). The occurrence of HIV type 1 (HIV-1) infection is found to be accelerated in people infected with Mycobacterium tuberculosis, but the mechanism by which mycobacterial protein(s) induces HIV-1 LTR trans-activation is not clearly understood. We show here that the M. tuberculosis proline-proline-glutamic acid (PPE) protein Rv1168c (PPE17) can augment transcription from HIV-1 LTR in monocyte/macrophage cells. Rv1168c interacts specifically with Toll-like receptor-2 (TLR2) resulting in downstream activation of nuclear factor-κB (NF-κB) resulting in HIV-1 LTR trans-activation. Another PPE protein, Rv1196 (PPE18), was also found to interact with TLR2 but had no effect on HIV-1 LTR trans-activation because of its inability to activate the NF-κB signaling pathway. In silico docking analyses and mutation experiments have revealed that the N-terminal domain of Rv1168c specifically interacts with LRR motifs 15-20 of TLR2, and this site of interaction is different from that of Rv1196 protein (LRR motifs 11-15), indicating that the site of interaction on TLR2 dictates the downstream signaling events leading to activation of NF-κB. This information may help in understanding the mechanism of pathogenesis of HIV-1 during M. tuberculosis co-infection.

Item Type: Article
Additional Information: [Open Access from the Publisher]
Depositing User: Dr P Divakar
Date Deposited: 04 Sep 2015 11:09
Last Modified: 22 Sep 2016 15:53
URI: http://cdfd.sciencecentral.in/id/eprint/477

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