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Journal of Virology, September 2001, p. 8390-8399, Vol. 75, No. 18
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.18.8390-8399.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
A Preponderance of CCR5+
CXCR4+ Mononuclear Cells Enhances Gastrointestinal Mucosal
Susceptibility to Human Immunodeficiency Virus Type 1 Infection
Michael A.
Poles,*
Julie
Elliott,
Philip
Taing,
Peter A.
Anton, and
Irvin S. Y.
Chen
Department of Medicine, UCLA School of
Medicine, UCLA Center for HIV and Digestive Diseases, and UCLA AIDS
Institute, Los Angeles, California 90095
Received 2 April 2001/Accepted 5 June 2001
The gastrointestinal mucosa harbors the majority of the body's
CD4+ cells and appears to be uniquely susceptible to human
immunodeficiency virus type 1 (HIV-1) infection. We undertook this
study to examine the role of differences in chemokine receptor
expression on infection of mucosal mononuclear cells (MMCs) and
peripheral blood mononuclear cells (PBMCs) by R5- and X4-tropic HIV-1.
We performed in vitro infections of MMCs and PBMCs with R5- and
X4-tropic HIV-1, engineered to express murine CD24 on the infected
cell's surface, allowing for quantification of HIV-infected cells and
their phenotypic characterization. A greater percentage of MMCs than
PBMCs are infected by both R5- and X4-tropic HIV-1. Significant
differences exist in terms of chemokine receptor expression in the
blood and gastrointestinal mucosa; mucosal cells are predominantly
CCR5+ CXCR4+, while these cells make up less
than 20% of the peripheral blood cells. It is this cell population
that is most susceptible to infection with both R5- and X4-tropic HIV-1
in both compartments. Regardless of whether viral isolates were derived
from the blood or mucosa of HIV-1-infected patients, HIV-1 p24
production was greater in MMCs than in PBMCs. Further, the chemokine
receptor tropism of these patient-derived viral isolates did not differ between compartments. We conclude that, based on these findings, the
gastrointestinal mucosa represents a favored target for HIV-1, in part
due to its large population of CXCR4+ CCR5+
target cells and not to differences in the virus that it contains.
*
Corresponding author. Mailing address: Center for HIV
and Digestive Diseases, Division of Digestive Diseases, Department of Medicine, UCLA School of Medicine, 1529 McDonald Research Laboratories, 675 Charles E. Young Dr. South, Los Angeles, CA 90095. Phone: (310) 794-7195. Fax: (310) 267-0289. E-mail: mpoles{at}ucla.edu.
Journal of Virology, September 2001, p. 8390-8399, Vol. 75, No. 18
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.18.8390-8399.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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