A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection.
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.
Poles
M A
MA
Department of Medicine, UCLA School of Medicine, UCLA Center for HIV and Digestive Diseases, Los Angeles, California 90095, USA. mpoles@ucla.edu
Elliott
J
J
Taing
P
P
Anton
P A
PA
Chen
I S
IS
D005753:Gastric Mucosa / Q000473:pathology / Q000821:virology*; D015658:HIV Infections / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000378:metabolism*; D014779:Virus Replication
D019713:Receptors, CCR5; D019718:Receptors, CXCR4