RGD Reference Report - Mycobacterium tuberculosis-induced CXCR4 and chemokine expression leads to preferential X4 HIV-1 replication in human macrophages.

General

Mycobacterium tuberculosis-induced CXCR4 and chemokine expression leads to preferential X4 HIV-1 replication in human macrophages.
Authors:	Hoshino, Y Tse, DB Rochford, G Prabhakar, S Hoshino, S Chitkara, N Kuwabara, K Ching, E Raju, B Gold, JA Borkowsky, W Rom, WN Pine, R Weiden, M
Citation:	Hoshino Y, etal., J Immunol. 2004 May 15;172(10):6251-8.
RGD ID:	4892112
Pubmed:	PMID:15128813 (View Abstract at PubMed)
Opportunistic infections such as pulmonary tuberculosis (TB) increase local HIV-1 replication and mutation. As AIDS progresses, alteration of the HIV-1 gp120 V3 sequence is associated with a shift in viral coreceptor use from CCR5 (CD195) to CXCR4 (CD184). To better understand the effect of HIV/TB coinfection, we screened transcripts from bronchoalveolar lavage cells with high density cDNA arrays and found that CXCR4 mRNA is increased in patients with TB. Surprisingly, CXCR4 was predominately expressed on alveolar macrophages (AM). Mycobacterium tuberculosis infection of macrophages in vitro increased CXCR4 surface expression, whereas amelioration of disease reduced CXCR4 expression in vivo. Bronchoalveolar lavage fluid from TB patients had elevated levels of CCL4 (macrophage inflammatory protein-1beta), CCL5 (RANTES), and CX3CL1 (fractalkine), but not CXCL12 (stromal-derived factor-1alpha). We found that M. tuberculosis infection of macrophages in vitro increased viral entry and RT of CXCR4-using [corrected] HIV-1, but not of CCR5-using [corrected] HIV-1. Lastly, HIV-1 derived from the lung contains CD14, suggesting that they were produced in AM. Our results demonstrate that TB produces a permissive environment for replication of CXCR4-using virus by increasing CXCR4 expression in AM and for suppression of CCR5-using HIV-1 by increasing CC chemokine expression. These changes explain in part why TB accelerates the course of AIDS. CXCR4 inhibitors are a rational therapeutic approach in HIV/TB coinfection.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
pulmonary tuberculosis		IEP		4892112	mRNA:increased expression:lung (human)	RGD
pulmonary tuberculosis		ISO	CCL5 (Homo sapiens)	4892112; 4892112	mRNA:increased expression:lung (human)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Ccl5 (C-C motif chemokine ligand 5)

Genes (Mus musculus)

Ccl5 (C-C motif chemokine ligand 5)

Genes (Homo sapiens)

CCL5 (C-C motif chemokine ligand 5)

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Mycobacterium tuberculosis-induced CXCR4 and chemokine expression leads to preferential X4 HIV-1 replication in human macrophages.