Bouhlal Hicham, Chomont Nicolas, Haeffner-Cavaillon Nicole, Kazatchkine Michel D, Belec Laurent, Hocini Hakim
Institut National de la Santé et de la Recherche Médicale, Unité 430, and Université Pierre et Marie Curie, Paris, France.
J Immunol. 2002 Sep 15;169(6):3301-6. 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.
在本研究中,我们证明X4嗜性和R5嗜性的HIV-1毒株均能够感染人上皮细胞系HT-29。在HIV与细胞培养物接触之前将其添加到精液中时,感染增强了2倍。精液的增强作用依赖补体,这可通过对精液进行加热或EDTA处理来阻断精液中C3a/C3a(去精氨酸)的产生以及用针对补体受体3型(CD11b/CD18)和可溶性CD16的单克隆抗体抑制精液依赖性增强作用来证明。通过培养物中p24抗原的释放以及HIV-1 pol基因的半定量PCR来评估HT-29细胞的感染情况。与未调理的病毒相比,在精液调理的X4嗜性和R5嗜性病毒的情况下,基质细胞衍生因子1对HT-29感染的抑制作用降低。相反,与未调理的病毒相比,调理的X4嗜性HIV-1对RANTES感染的抑制作用增强。综上所述,这些观察结果表明,精液中补体的激活可能通过促进上皮细胞感染和/或增强粘膜中表达补体受体的靶细胞感染,在HIV-1的粘膜传播中发挥增强作用。