Opsonization of HIV-1 by Semen Complement Enhances Infection of Human Epithelial Cells

• Published in: The Journal of immunology (1950) 2002-09, Vol.169 (6), p.3301-3306
• Main Authors: Bouhlal, Hicham, Chomont, Nicolas, Haeffner-Cavaillon, Nicole, Kazatchkine, Michel D, Belec, Laurent, Hocini, Hakim
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - physiology; Complement Activation - immunology; Complement System Proteins - metabolism; Complement System Proteins - physiology; Disease Susceptibility - immunology; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - pathogenicity; HT29 Cells - immunology; HT29 Cells - metabolism; HT29 Cells - virology; Humans; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - virology; Macrophage-1 Antigen - physiology; Opsonin Proteins - metabolism; Receptors, Chemokine - physiology; Receptors, Complement - biosynthesis; Receptors, HIV - biosynthesis; Semen - immunology; Semen - metabolism; Semen - virology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.6.3301

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.