Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection

Akhil Maheshwari, Lesley E. Smythies, Xiaoyun Wu, Lea Novak, Ronald Clements, Devin Eckhoff, Audrey J Lazenby, William J. Britt, Phillip D. Smith

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1111-1117
Number of pages7
JournalJournal of Leukocyte Biology
Volume80
Issue number5
DOIs
StatePublished - Nov 1 2006

Fingerprint

Cytomegalovirus
HIV Infections
HIV-1
Down-Regulation
Macrophages
Colitis
Conditioned Culture Medium
Cytokines
Permissiveness
Human Immunodeficiency Virus Proteins
Vesicular Stomatitis
Aptitude
Viral Proteins
Monocytes
Anti-Idiotypic Antibodies
Glycoproteins
Colon
Acquired Immunodeficiency Syndrome
Proteins
Viruses

Keywords

  • Extracellular matrix
  • Intestinal macrophage
  • Mucosa
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Maheshwari, A., Smythies, L. E., Wu, X., Novak, L., Clements, R., Eckhoff, D., ... Smith, P. D. (2006). Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection. Journal of Leukocyte Biology, 80(5), 1111-1117. https://doi.org/10.1189/jlb.0306230

Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection. / Maheshwari, Akhil; Smythies, Lesley E.; Wu, Xiaoyun; Novak, Lea; Clements, Ronald; Eckhoff, Devin; Lazenby, Audrey J; Britt, William J.; Smith, Phillip D.

In: Journal of Leukocyte Biology, Vol. 80, No. 5, 01.11.2006, p. 1111-1117.

Research output: Contribution to journalArticle

Maheshwari, A, Smythies, LE, Wu, X, Novak, L, Clements, R, Eckhoff, D, Lazenby, AJ, Britt, WJ & Smith, PD 2006, 'Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection', Journal of Leukocyte Biology, vol. 80, no. 5, pp. 1111-1117. https://doi.org/10.1189/jlb.0306230
Maheshwari, Akhil ; Smythies, Lesley E. ; Wu, Xiaoyun ; Novak, Lea ; Clements, Ronald ; Eckhoff, Devin ; Lazenby, Audrey J ; Britt, William J. ; Smith, Phillip D. / Cytomegalovirus blocks intestinal stroma-induced down-regulation of macrophage HIV-1 infection. In: Journal of Leukocyte Biology. 2006 ; Vol. 80, No. 5. pp. 1111-1117.
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