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

Abstract

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/C3adesArg 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.

Opsonization of HIV with Complement Enhances Infection of Dendritic Cells and Viral Transfer to CD4 T Cells in a CR3 and DC-SIGN-Dependent Manner

“…In addition, proviral HIV-1 DNA was detected in iDC within 6 h of incubation with complement-opsonized HIV-1, the amounts of HIV-1 pol DNA measured by semiquantitative nested PCR being significantly higher in cells infected with opsonized HIV, as compared with cells infected with virus that had been preincubated with culture medium. These data extend previous observations on the enhancing effect of complement on infection of monocytes/macrophages (8, 9) and more recently of CD4-negative, complement receptor-positive epithelial cells (10). The role of complement receptor (CR3) was shown by the blocking effect of anti-CR3 mAbs on infection of iDC with opsonized HIV-1 BaL and HIV-1 NDK .…”

“…Opsonization of HIV-1 with complement results in enhancement of viral infection of T and B cell lines (6,7), primary PBMC (8), and primary monocytes/ macrophages (9). We have demonstrated that HIV particles activate complement in semen resulting in an ability to infect human CD4-negative epithelial cells in a complement-dependent fashion via CD11b/CD18 (CR3) (10). Recently, others have reported a crucial role of CR3 in the productive infection of dendritic cells (DC) 3 by C3-opsonized HIV (11).…”

Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models

“…An aliquot of semen was heat-inactivated (HI) for 30 min at 56 uC. Virus, either HIV-1 BaL or HIV-1 RF was then incubated with fresh semen, used at a concentration of 25 %, HI semen or media for 1 h at 37 uC as previously described (Bouhlal et al, 2002). TZM-bl were seeded as described above and exposed to various concentrations of CV-N for 1 h prior to infection.…”

“…Inhibition of HIV-1 BaL and HIV-1 RF by CV-N was tested using TZM-bl cells, in the presence or absence of whole semen [used at final concentration of 12.5 % (v/v)]. HI of semen was performed in order to assess if any of the complement components had an effect on CV-N efficacy, since it is known that virus opsonization can enhance virus infectivity (Bouhlal et al, 2002).…”

CD46 (Membrane Cofactor Protein) Acts as a Human Epithelial Cell Receptor for Internalization of Opsonized Uropathogenic Escherichia coli

“…Less is known about the ability of C3-opsonized pathogens to interact with receptors on epithelial cells, and the functional consequence of such C3-receptor-ligand interaction. Colonic and cervical epithelial cells can internalize opsonized HIV (20) and Neisseria gonorrhoea (21), respectively. This occurs through binding to CR3.…”