Soluble CD16 inhibits CR3 (CD11b/CD18)-mediated infection of monocytes/macrophages by opsonized primary R5 HIV-1

We demonstrate that soluble CD16 (sCD16; soluble Fc gamma RIII), a natural ligand of CR3, inhibits the infection of monocytes by primary R5 HIV-1 stra in opsonized with serum of seronegative individuals. Inhibition of monocyte infection by sCD16 was similar to that observed with anti-CR3 mAbs, indica ting that opsonized HIV may use a CR3-dependent pathway for entry in monocy tic cells. Cultured human monocytes express both CR3 (CD11b/CD18) and CCR5 receptors, RANTES, the natural ligand of CCR5, inhibited infection of monoc ytes with unopsonized HIV particles and partially that of monocytes infecte d with HIV particles opsonized with complement-derived fragments. Although HIV-infected monocytes from homozygous CCR5 Delta 32/Delta 32 (CCR5(-/-)) i ndividuals produce low levels of p24, cells infected with opsonized particl es produced higher levels of p24 than cells infected with unopsonized parti cles, Our results thus suggest that CR3 mag represent an alternative corece ptor to CCR5 of opsonized primary R5 virus entry into monocytes/macrophages . We also observed that the concentration of sCD16 is greatly decreased in sera of HIV-infected patients with low lymphocyte CD4(+) counts. Taken toge ther, our findings suggest that sCD16, present in plasma, may play an impor tant role in controlling HIV-1 spread.