gp340 Promotes Transcytosis of Human Immunodeficiency Virus Type 1 in Genital Tract-Derived Cell Lines and Primary Endocervical Tissue

Abstract

The human scavenger receptor gp340 has been identified as a binding protein for the human immunodeficiency virus type 1 (HIV-1) envelope that is expressed on the cell surface of female genital tract epithelial cells. This interaction allows such epithelial cells to efficiently transmit infective virus to susceptible targets and maintain viral infectivity for several days. Within the context of vaginal transmission, HIV must first traverse a normally protective mucosa containing a cell barrier to reach the underlying T cells and dendritic cells, which propagate and spread the infection. The mechanism by which HIV-1 can bypass an otherwise healthy cellular barrier remains an important area of study. Here, we demonstrate that genital tract-derived cell lines and primary human endocervical tissue can support direct transcytosis of cell-free virus from the apical to basolateral surfaces. Further, this transport of virus can be blocked through the addition of antibodies or peptides that directly block the interaction of gp340 with the HIV-1 envelope, if added prior to viral pulsing on the apical side of the cell or tissue barrier. Our data support a role for the previously described heparan sulfate moieties in mediating this transcytosis but add gp340 as an important facilitator of HIV-1 transcytosis across genital tract tissue. This study demonstrates that HIV-1 actively traverses the protective barriers of the human genital tract and presents a second mechanism whereby gp340 can promote heterosexual transmission.

The Calcium-induced Conformation and Glycosylation of Scavenger-rich Cysteine Repeat (SRCR) Domains of Glycoprotein 340 Influence the High Affinity Interaction with Antigen I/II Homologs

“…Although GP340 acted as a clearance mechanism in the oral cavity, the case was very different on the vaginally derived GP340, which is immobilized on the cell surface, where this was shown to mediate transcytosis from apical to basolateral surface in both genital tract epithelial cells in culture and with endocervical tissue (52). Similarly, in SPR experiments, immobilized SRCRs adhere tightly to AgI/II homologs, and in the fluid phase SRCRs aggregate S. mutans and S. gordonii, a double-faceted property, where on the one hand it acts as a portal of entry for microbes while immobilized and on the other hand as a clearance mechanism within the oral cavity in fluid state.…”

REVIEW ARTICLE: HIV Infection in the Female Genital Tract: Discrete Influence of the Local Mucosal Microenvironment

“…47,50 A variant of salivary agglutinin named gp340, which is expressed on cervical and vaginal ECs, has also been implicated in the passage of HIV through the epithelium. 54,55 The relative contribution of these receptors to HIV entry and infection in genital ECs is unclear.…”

Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

“…Expression of the HIV coreceptors GalCer, HSPG, CXCR4, and CCR5 and their functional role in viral transmission have been demonstrated in endometrial, vaginal, and intestinal epithelial cells (2,3,14,19,20,28,34,43,51,54,63,64). Reductions in cell-free HIV transmission through the fetal oral epithelium by antibodies against GalCer and HSPG (Fig.…”