Soluble CD16 Inhibits CR3 (CD11b/CD18)-Mediated Infection of Monocytes/Macrophages by Opsonized Primary R5 HIV-1

Self Cite

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.

Section: Discussionsupporting

confidence: 79%

Section: Opsonization Of Hiv-1 By Semen Complement Enhances Infectionmentioning

confidence: 99%

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

Bouhlal

Chomont

Haeffner‐Cavaillon

et al. 2002

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“…We also found that productive infection was strongly inhibited by anti-CD4 mAb (data not shown), suggesting that even in CR3-mediated enhancement of productive infection CD4 plays a critical role. In other studies, inhibition by anti-CR3 mAb of monocyte infection (18,22) and partial inhibition by CD11b-specific Abs (10) of PBMC infection with HIV were observed.…”

Section: Discussionmentioning

confidence: 99%

“…Infection of human monocytes and macrophages with HIV is greatly facilitated by opsonization of the virus with C3 fragments (5,22). To test whether infection of imMDCs by HIV is influenced by opsonization, the cells were cultured with the HIV-1 primary isolate pretreated with IgG and complement.…”

Section: Effect Of Opsonization Of Hiv By Complement On Infection Of mentioning

confidence: 99%

Cutting Edge: Productive HIV-1 Infection of Dendritic Cells via Complement Receptor Type 3 (CR3, CD11b/CD18)

Bajtay

Speth

Erdei

et al. 2004

In the present study, we demonstrate that macrophage-tropic HIV-1 opsonized by complement and limited amounts of anti-HIV-IgG causes up to 10-fold higher productive infection of human monocyte-derived dendritic cells than HIV treated with medium or HIV opsonized by Ab only. Enhanced infection is completely abolished by a mAb specific for the ligand-binding site of CD11b (i.e., α-chain of complement receptor 3, receptor for iC3b), proving the importance of complement receptor 3 in this process. Inhibition of complement activation by EDTA also prevents enhanced infection, further demonstrating the role of complement in virus uptake and productive infection. Since HIV is, even in the absence of Abs, regularly opsonized by complement, most probably the above-described mechanism plays a role during in vivo primary infection.

“…Semen, cervicovaginal secretions, and breast milk contain complement proteins that may allow viral particles to be opsonized (3)(4)(5). 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).…”

mentioning

confidence: 99%

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

Bouhlal

Chomont

Requena

et al. 2007

Self Cite

In the present study, we demonstrated that opsonization of primary HIV-1 with human complement enhances infection of immature monocyte-derived dendritic cells (iDC) and transmission in trans of HIV to autologous CD4+ T lymphocytes. Infection of iDC by opsonized primary R5- and X4-tropic HIV was increased 3- to 5-fold as compared with infection by the corresponding unopsonized HIV. Enhancement of infection was dependent on CR3 as demonstrated by inhibition induced by blocking Abs. The interaction of HIV with CCR5 and CXCR4 on iDC was affected by opsonization. Indeed, stromal-derived factor-1 was more efficient in inhibiting infection of iDC with opsonized R5-tropic HIV-1BaL (45%) than with heat-inactivated complement opsonized virus and similarly RANTES inhibited more efficiently infection of iDC with opsonized X4-tropic HIV-1NDK (42%) than with heat-inactivated complement opsonized virus. We also showed that attachment of complement-opsonized virus to DC-specific ICAM-grabbing nonintegrin (DC-SIGN) molecule on iDC and HeLa DC-SIGN+ CR3− cells was 46% and 50% higher compared with heat-inactivated complement opsonized virus, respectively. Hence, Abs to DC-SIGN suppressed up to 80% and 60% the binding of opsonized virus to HeLa cells and iDC, respectively. Furthermore, Abs to DC-SIGN inhibited up to 70% of the infection of iDC and up to 65% of infection in trans of autologous lymphocytes with opsonized virus. These results further demonstrated the role of DC-SIGN in complement opsonized virus uptake and infection. Thus, the virus uses complement to its advantage to facilitate early steps leading to infection following mucosal transmission of HIV.