gp120-Independent HIV Infection of Cells Derived From the Female Reproductive Tract, Brain, and Colon

Abstract

The infection of CD4 cells may have significant involvement in the transmission and long-term persistency of HIV. Using HIV clones carrying the enhanced green fluorescent protein (EGFP), we infected epithelial and glioneuronal cell lines derived from the female reproductive tract, brain, colon, and intestine. HIV infection was quantified by counting EGFP-positive cells. Infection was quantified in cell lines from the female reproductive tract, brain tissue, and colon tissue (0.36%-3.15%). Virus replicated in the infected cells and the progeny virus were infectious for CD4 cells, HeLa-CD4, and CEM T lymphocytes. Furthermore, we found that infection of these epithelial and brain cell lines is independent of gp120. The results from the infection of CD4 epithelial cells suggest that HIV can traverse epithelial cell layers by infecting them through a gp120-independent mechanism. Infection of glial and neuronal cell lines suggests that HIV infection of these cells is a probable mechanism for HIV pathogenicity in the brain and a possible cause for persistent infection in patients.

Transcytosis of HIV-1 through Vaginal Epithelial Cells Is Dependent on Trafficking to the Endocytic Recycling Pathway

“…The role of HIV-1 envelope for viral entry into epithelial cells remains controversial. While some reports argue that HIV-1 envelope is not needed for entry into epithelial cells [36] [37], others suggest that it is needed [8], [38], [39]. Our experiment demonstrated that HIV-1 could enter vaginal epithelial cells without envelope, aiding in the conclusion that a factor other than envelope plays a role in the differential trafficking of native and heat-inactivated virus.…”

“…While some reports argue that HIV-1 envelope is not needed for entry into epithelial cells [36] [37], others suggest that it is needed [8], [38], [39]. We also tried to address this issue in our system.…”

Emerging Roles of Prostaglandins in HIV-1 Transcription

“…It has been proposed that HIV-1 can cross the epithelium barrier via epithelial cell infection. A quantitative analysis of enhanced green fluorescent protein-tagged HIV infection of cells derived from the female reproductive tract, brain and colon demonstrated that gp120-independent HIV infection occurs in intestinal epithelial cells (Zheng et al, 2006). These results clearly illustrate the importance of such cells in viral latency and transmission during mucosal HIV-1 infection.…”

“…Also, primary human intestinal cells are capable of selectively transferring R5 HIV-1 to CCR5+ cells (cells that express both GalCer and CCR5 on their cell surface) (Meng et al, 2002). Thus, they proposed that infection of epithelial cells might facilitate HIV-1 penetration into the epithelium barrier (Zheng et al, 2006). Following viral replication in the infected epithelial cells, newly formed HIV virions may be discharged into the basolateral side of the epithelium and exposed to immune cells present in the mucosal milieu.…”

“…The potent anti-inflammatory molecule 15-d-PGJ 2 strongly suppresses HIV-1 replication and particle production in Caco-2 cells, a human intestinal cell line that mimics rectal epithelium susceptible to HIV-1 (Delezay et al, 1997;Fantini et al, 1991;Fantini et al, 1992;Fantini et al, 1993;Zheng et al, 2006). Prophylactic or co-treatment with 15-d-PGJ 2 of intestinal epithelial cells significantly reduces HIV replication as well as p24 core antigen production (Boisvert et al, 2008).…”