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Regulation of HIV receptor expression in cervical epithelial cells by Gram-negative bacterial lipopolysaccharide

Kurt J Sales, Timothy Klein, Arieh A Katz

Abstract


Background. Sexually transmitted infections (STIs) caused by the Gram-negative bacteria Chlamydia trachomatis and Neisseria gonorrhoeae are associated with an increased risk of HIV acquisition in South African women. HIV infection involves binding of the virus to CD4+ receptors on host cells and subsequent binding to a chemokine co-receptor that mediates fusion with the host target cell membrane.

Objective. To investigate the potential impact of STIs on HIV receptor expression in cervical epithelial cells, and the molecular pathways mediating this effect.

Methods. Expression of Toll-like receptor 4 (TLR4), CD4+ and CCR5 was investigated in HPV type 18-positive (HeLa) and HPV-negative (C33A) cervical epithelial cells, uterine adenocarcinoma cells (Ishikawa), cervical squamous cell carcinoma tissue and normal cervical tissue by real-time polymerase chain reaction (RT-PCR) analysis. HIV receptor expression in HeLa cells was investigated in the presence/absence of 10 µg/ml bacterial lipopolysaccharide (LPS) and chemical inhibitors of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK1/2) or cyclo-oxygenase-2 (COX-2) by RT-PCR analysis.

Results. TLR4, CD4+ and CCR5 expression was elevated in HeLa, C33A and Ishikawa cell lines and carcinoma tissue, compared with normal cervical tissue. Treatment of HeLa cells with LPS increased expression of the primary HIV chemokine co-receptor CCR5 (p<0.01) and several alternative HIV receptors including CCR2b (p<0.01), CXCR6 (p<0.05) and GPR1 (p<0.05), but not CD4+. We found that LPS-mediated CCR5 expression occurred via induction of the EGFR, ERK1/2 and COX-2 signalling pathways.

Conclusion. Our findings suggest that STIs have the potential to enhance susceptibility to HIV infection in women by regulating expression of HIV receptors in cervical epithelial cells.

Authors' affiliations

Kurt J Sales, MRC/UCT Receptor Biology Research Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, South Africa

Timothy Klein, MRC/UCT Receptor Biology Research Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, South Africa

Arieh A Katz, MRC/UCT Receptor Biology Research Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, South Africa

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Keywords

Lipopolysaccharide; HIV; Receptor; Signalling; Bacteria

Cite this article

South African Medical Journal 2015;105(1):56-61. DOI:10.7196/SAMJ.8185

Article History

Date submitted: 2014-03-13
Date published: 2014-11-21

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