HIV coreceptor and chemokine ligand gene expression in the male urethra and female cervix

McClure, C. Patrick; Tighe, Patrick J.; Robins, R. A.; Bansal, Deepa; Bowman, Christine; Kingston, Margaret; Ball, Jonathan K.

doi:10.1097/01.aids.0000180096.50393.96

Cited by 19 publications

(23 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of B cells has been taken by some to denote contamination by systemic blood [19]; however, our protocol aimed to disqualify any specimens presenting visible blood. It should be noted that others have found B lymphocytes in similar abundance, or even in excess of HIV-susceptible cells in previous genital tract studies [7].Our findings of parity between CCR5 and CXCR4 expression on all cellular denominations except for CD14 cells are in agreement with the findings of many studies [12,13,20,23] and at odds with others [11]. Discrepancy in the role of chemokine receptor expression in selective HIV transmission can largely be explained by variable anatomical sampling sites, methods of sampling and choice of assays and associated sensitivities in detection.…”

supporting

confidence: 93%

“…Patterson and colleagues conducted a landmark study on ectocervical punch biopsies [11], finding a ten-fold elevation of CCR5 over CXCR4. In contrast, we and others have aimed to sample only the outer cervical epithelia as representative of the initial cellular barrier faced by seminal HIV-1 [10,12,13]. We found an excess cervical expression of CXCR4 above CCR5 [12], which was supported by the tissue-based immunohistochemical analysis of others [13].…”

Section: Introductionsupporting

confidence: 63%

“…In contrast, we and others have aimed to sample only the outer cervical epithelia as representative of the initial cellular barrier faced by seminal HIV-1 [10,12,13]. We found an excess cervical expression of CXCR4 above CCR5 [12], which was supported by the tissue-based immunohistochemical analysis of others [13].Ex vivo organ culture of infection across the genital tract has provided further insight into natural HIV infection, suggesting Langerhans and T cells within female genital epithelia as the earliest targets of infection, via endocytosis and director receptor-mediated fusion, respectively [14]. Other ex vivo organ culture systems have also indicated productive infection of cervical subepithelial macrophages in addition to further detection of HIV in Langerhans and T cells (summarized in [5]).…”

mentioning

confidence: 99%

See 2 more Smart Citations

HIV‐1 co‐receptor expression and epithelial immune cells of the cervix in asymptomatic women attending a genitourinary medicine clinic

et al. 2012

View full text Add to dashboard Cite

ObjectivesThe aim of the study was to qualitatively and semiquantitatively characterize the expression of the principal HIV co-receptors chemokine (C-C motif) receptor 5 (CCR5) and chemokine (C-X-C motif) receptor 4 (CXCR4) on susceptible CD4 T-helper cell, monocyte/macrophage and Langerhans dendritic cell populations within the cervical epithelia of asymptomatic women attending a genitourinary medicine clinic. MethodsOf 77 asymptomatic women recruited, 35 were excluded: 21 because they were found to have bacterial vaginosis, eight because they were found to have candida and six for other reasons. Cervical cytobrush samples from 11 women with Chlamydia trachomatis infection and 31 women without any detectable genital infection were stained with fluorescently labelled antibodies specific for cell surface CCR5, CXCR4, CD4, CD3, CD1a and CD19 expression, then analysed by flow cytometry. Results CD4/CD3 T-helper cells (84%), CD1aLangerhans dendritic cells (75%) and CD4/CD14 monocytes/macrophages (59%) were detected in the samples. CCR5 and CXCR4 HIV co-receptor expression was observed on 46-86% of the above subsets. CD1a cells exhibited significantly higher CCR5 and CXCR4 positivity and median fluorescence than CD4 cells and higher CXCR4 positivity and median fluorescence than CD14 cells (P < 0.05 or less). Increased detection of CCR5 over CXCR4 was seen in CD14 cells (P < 0.05). No significant differences in CCR5 or CXCR4 expression were found in samples from asymptomatic women with or without chlamydial infection. ConclusionsCo-receptor expression confirms the potential for CD1a Langerhans cells, monocytes/macrophages and T-helper cells in the cervix as primary targets for HIV infection. Previously observed selective transmission of CCR5-tropic isolates cannot be accounted for by a lack of CXCR4-expressing CD4 cervical immune cells. We were unable to identify any specific impact of chlamydial infection on co-receptor expression in this study. . Cellular fusion and entry of HIV-1 virions require co-expression of the principal CD4 receptor and either the chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) co-receptor [3,4]. Macrophages, T cells and Langerhans dendritic cells within the genital tract should thus potentially constitute a primary route of entry into uninfected people [5]. Indeed, characterization of the female genital epithelia has detailed HIV susceptibility of all tissue types (vagina, ectocervix, transformation zone and endocervix), by a range of mechanisms (receptor-mediated fusion, transcytosis, endocytosis, and direct breach of damaged epithelia) (reviewed in [5,6]). However, the cervical transformation zone and adjacent endocervical canal have been hypothesized as the focal point for immune cell presence and thus also de novo HIV entry [7,8].Data on chemokine expression on cervical immune cells are limited. Endocervical epithelial T-cell expression of CCR5 has been observed at a higher level than in peripheral blood [9], and others have observed marginally highe...

show abstract

supporting

confidence: 93%

Section: Introductionsupporting

confidence: 63%

mentioning

confidence: 99%

See 1 more Smart Citation

HIV‐1 co‐receptor expression and epithelial immune cells of the cervix in asymptomatic women attending a genitourinary medicine clinic

et al. 2012

View full text Add to dashboard Cite

show abstract

“…In contrast, GPR1, GPR15, and APJ are not known to be expressed on CD4 ϩ T lymphocytes, although GPR1 is expressed on and reportedly supports in vitro HIV-1 infection of several nonlymphoid target cells (51,54). Within the genital tract, CCR2 and CCR3 are expressed in both female and male genital mucosa (36,41) although little is known about mucosal tissue expression of the other GPCRs used by HIV-1. However, no alternative coreceptor was used by recipient viruses more efficiently than by donor viruses, as a group, and while some individual transmission pairs showed significant donor/recipient differences for individual coreceptors, there was no consistent pattern among the pairs.…”

Section: Discussionmentioning

confidence: 99%

Heterosexual Transmission of Human Immunodeficiency Virus Type 1 Subtype C: Macrophage Tropism, Alternative Coreceptor Use, and the Molecular Anatomy of CCR5 Utilization

Isaacman-Beck

Hermann

et al. 2009

J Virol

104

View full text Add to dashboard Cite

Human immunodeficiency virus type 1 transmission selects for virus variants with genetic characteristics distinct from those of donor quasispecies, but the biological factors favoring their transmission or establishment in new hosts are poorly understood. We compared primary target cell tropisms and entry coreceptor utilizations of donor and recipient subtype C Envs obtained near the time of acute infection from Zambian heterosexual transmission pairs. Both donor and recipient Envs demonstrated only modest macrophage tropism, and there was no overall difference between groups in macrophage or CD4 T-cell infection efficiency. Several individual pairs showed donor/recipient differences in primary cell infection, but these were not consistent between pairs. Envs had surprisingly broad uses of GPR15, CXCR6, and APJ, but little or no use of CCR2b, CCR3, CCR8, GPR1, and CXCR4. Donors overall used GPR15 better than did recipients. However, while several individual pairs showed donor/recipient differences for GPR15 and/or other coreceptors, the direction of the differences was inconsistent, and several pairs had unique alternative coreceptor patterns that were conserved across the transmission barrier. CCR5/CCR2b chimeras revealed that recipients as a group were more sensitive than were donors to replacement of the CCR5 extracellular loops with corresponding regions of CCR2b, but significant differences in this direction were not consistent within pairs. These data show that sexual transmission does not select for enhanced macrophage tropism, nor for preferential use of any alternative coreceptor. Recipient Envs are somewhat more constrained than are donors in flexibility of CCR5 use, but this pattern is not universal for all pairs, indicating that it is not an absolute requirement.A majority of new human immunodeficiency virus type 1 (HIV-1) infections are initiated by only a single genetic species, although in some, several closely related variants are transmitted (19,26,34,44,55). Nevertheless, in all cases, a molecular bottleneck occurs during transmission (8,15,22,33,56). This bottleneck does not appear to be simply a stochastic result of low-efficiency transmission since viral sequences in recipients do not typically reflect the majority sequences in donors, even in genital secretions responsible for transmission (22,56). Identifying the biological factors that favor particular variants in transmission and/or establishment in new hosts is essential both to understanding the mechanisms of transmission and to developing approaches, including vaccines and microbicides, that might interrupt transmission.More than 15 years ago, it was recognized that new infections were nearly always initiated by HIV-1 variants that were macrophage tropic and non-syncytium inducing (NSI) in T-cell lines, even though donors often harbored variants that were syncytium inducing (SI) and non-macrophage tropic (55). The molecular basis for these characteristics was subsequently linked to use of the entry coreceptor CCR5 by macrophagetropic/...

show abstract

“…While the majority of HIV-1-susceptible cells, including TZM-bl cells, a derivative from HeLa cervical ECs, express CD4, CCR5, and CXCR4 (54,79), primary genital ECs express only CXCR4 and CCR5 (41), but not CD4 (8). However, both cell types remain permissive to HIV-1 attachment/entry and transmigration (8,41), indicating that HIV-1 can utilize alternative cellular molecules for these purposes. Indeed, primary genital ECs and the endometrial epithelial cell line HEC-1A express a number of alternative receptors, including proteoglycans (PG) with heparan sulfate (HSPG) or chondroitin sulfate (CSPG) chains (8,46), as well as galactosylceramide (GalCer) (24)(25)85), and mannose receptors (74).…”

mentioning

confidence: 99%

Anti-HIV-1 Activity of Elafin Is More Potent than Its Precursor's, Trappin-2, in Genital Epithelial Cells

Drannik

Nag

Yao

et al. 2012

J Virol

View full text Add to dashboard Cite

HIV coreceptor and chemokine ligand gene expression in the male urethra and female cervix

Abstract: The selective transmission of CCR5-tropic viral variants is unlikely to result simply from differential coreceptor abundance at the genital epithelia.

Cited by 19 publications

References 49 publications

HIV‐1 co‐receptor expression and epithelial immune cells of the cervix in asymptomatic women attending a genitourinary medicine clinic

HIV‐1 co‐receptor expression and epithelial immune cells of the cervix in asymptomatic women attending a genitourinary medicine clinic

Heterosexual Transmission of Human Immunodeficiency Virus Type 1 Subtype C: Macrophage Tropism, Alternative Coreceptor Use, and the Molecular Anatomy of CCR5 Utilization

Anti-HIV-1 Activity of Elafin Is More Potent than Its Precursor's, Trappin-2, in Genital Epithelial Cells

Contact Info

Product

Resources

About