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 typ e 1 (HIV-1) infection. We undertook this study to examine the role of diffe rences 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- a nd X4-tropic HIV-1, engineered to express murine CD24 on the infected cell' s surface, allowing for quantification of HIV-infected cells and their phen otypic characterization. A greater percentage of MMCs than PBMCs are infect ed 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 th at is most susceptible to infection with both R5- and X4-tropic HIV-1 in bo th compartments. Regardless of whether viral isolates were derived from the blood or mucosa of HIV-1-infected patients, HIV-1 p24 production was great er in MMCs than in PBMCs. Further, the chemokine receptor tropism of these patient-derived viral isolates did not differ between compartments. We conc lude 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.