Transepithelial transport of HIV-1 by M cells is receptor-mediated.
Human colon carcinoma Caco-2 cell monolayers undergo conversion into cells that share morphological and functional features of M cells when allowed to interact with B lymphocytes. A lymphotropic (X4) HIV-1 strain crosses M cell monolayers and infects underlying CD4(+) target cells. Transport requires both lactosyl cerebroside and CXCR4 receptors, which are expressed on the apical surface of Caco-2 and M cells. Antibodies specific for each receptor block transport. In contrast, a monotropic (R5) HIV-1 strain is unable to cross M cell monolayers and infect underlying monocytes, despite efficient transport of latex beads. Caco-2 and M cells do not express CCR5, but transfection of these cells with CCR5 cDNA restores transport of R5 virus, which demonstrates that HIV-1 transport across M cells is receptor-mediated. The follicle-associated epithelium covering human gut lymphoid follicles expresses CCR5, but not CXCR4, and lactosyl cerebroside, suggesting that HIV-1 infection may occur through M cells and enterocytes at these sites.
Fotopoulos
Grigorios
G
Swiss Institute for Experimental Cancer Research and Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
Harari
Alexandre
A
Michetti
Pierre
P
Trono
Didier
D
Pantaleo
Giuseppe
G
Kraehenbuhl
Jean-Pierre
JP
D001693:Biological Transport, Active; D018938:Caco-2 Cells; D018076:DNA, Complementary / Q000235:genetics; D020895:Enterocytes / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005699:Galactosylceramides / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D010581:Peyer's Patches / Q000378:metabolism / Q000821:virology; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology; D015728:Receptors, HIV / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D018076:DNA, Complementary; D005699:Galactosylceramides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV