Opsonization of HIV-1 by semen complement enhances infection of human epithelial cells.
In the present study we demonstrate that both X4- and R5-tropic HIV-1 strains are able to infect the human epithelial cell line HT-29. Infection was enhanced 2-fold when HIV was added to semen before contact with the cell cultures. The enhancing effect of semen was complement dependent, as evidenced by blockage of generation of C3a/C3a(desArg) in semen by heat or EDTA treatment of semen and suppression of semen-dependent enhancement with mAbs directed to complement receptor type 3 (CD11b/CD18) and soluble CD16. Infection of HT-29 cells was assessed by the release of p24 Ag in cultures and semiquantitative PCR of the HIV-1 pol gene. Inhibition of infection of HT-29 by stromal cell-derived factor 1 was decreased in the case of semen-opsonized X4- and R5-tropic virus compared with unopsonized virus. In contrast, inhibition of infection by RANTES was increased for opsonized X4-tropic HIV-1 compared with unopsonized virus. Taken together these observations indicate that activation of complement in semen may play an enhancing role in mucosal transmission of HIV-1 by facilitating infection of epithelial cells and/or enhancing infection of complement receptor-expressing target cells in the mucosa.
Bouhlal
Hicham
H
Institut National de la Santé et de la Recherche Médicale, Unité 430, and Université Pierre et Marie Curie, Paris, France.
Chomont
Nicolas
N
Haeffner-Cavaillon
Nicole
N
Kazatchkine
Michel D
MD
Belec
Laurent
L
Hocini
Hakim
H
D000276:Adjuvants, Immunologic / Q000502:physiology; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D004198:Disease Susceptibility / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D019073:HT29 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D009895:Opsonin Proteins / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000502:physiology; D011951:Receptors, Complement / Q000096:biosynthesis; D015728:Receptors, HIV / Q000096:biosynthesis; D012661:Semen / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D000276:Adjuvants, Immunologic; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D019707:Receptors, Chemokine; D011951:Receptors, Complement; D015728:Receptors, HIV; D003165:Complement System Proteins