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Cytomegalovirus blocks intestinal stroma‐induced down‐regulation of macrophage HIV‐1 infection
Author(s) -
Maheshwari Akhil,
Smythies Lesley E.,
Wu Xiaoyun,
Novak Lea,
Clements Ronald,
Eckhoff Devin,
Lazenby Audrey J.,
Britt William J.,
Smith Phillip D.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0306230
Subject(s) - proinflammatory cytokine , biology , macrophage , immunology , tumor necrosis factor alpha , cytokine , vesicular stomatitis virus , virology , chemokine , inflammation , virus , in vitro , biochemistry
Intestinal macrophages, unlike macrophages from other tissues, do not support HIV‐1 infection or produce proinflammatory cytokines. In vitro studies suggest this unique, functional phenotype is a result of the exposure of newly recruited blood monocytes to intestinal stromal products. However, in AIDS‐related CMV colitis, mucosal macrophages express HIV‐1 and proinflammatory cytokines. Therefore, we investigated the mechanism by which CMV confers permissiveness to HIV‐1 and cytokine production on intestinal macrophages. We show that intestinal stroma‐conditioned media (S‐CM) down‐regulated monocyte‐derived macrophage infection by HIV‐1 (pseudotyped with YU2 envelope or vesicular stomatitis virus glycoprotein) and production of TNF‐α, but preinfection of the cells with CMV reversed this down‐regulation, enhancing HIV‐1 infection, p24 production, and TNF‐α release. The ability of CMV to reverse S‐CM down‐regulation of macrophage HIV‐1 infection was blocked by anti‐TNF‐α antibodies and over‐ridden by exogenous TNF‐α. Immunohistochemical analysis of monocyte‐derived macrophages exposed to CMV and HIV‐1 (YU2 pseudotype) revealed that the cells infrequently contained CMV and HIV‐1 viral proteins. In addition, analysis of colon tissue sections from HIV‐1‐infected patients with CMV colitis showed that some macrophage‐like cells contained CMV and TNF‐α proteins, others contained HIV‐1 and TNF‐α proteins, but cells infrequently contained CMV and HIV‐1 proteins. These results indicate that CMV blocks stromal product inhibition of HIV‐1 infection in macrophages, and this inhibition is mediated, at least in part, by CMV‐induced TNF‐α acting in trans to enhance HIV‐1 infection.