Journal Article

Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection

Andrew W. Woodham, Julia R. Taylor, Andrew I. Jimenez, Joseph G. Skeate, Thomas Schmidt, Heike E. Brand, Diane M. Da Silva and W. Martin Kast

in Journal of Antimicrobial Chemotherapy

Volume 70, issue 6, pages 1686-1690
Published in print June 2015 | ISSN: 0305-7453
Published online February 2015 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkv045
Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection

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Objectives

High-risk human papillomavirus (HPV) infection leads to the development of several human cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is the most common of the cancer-causing genotypes and gains entry to the basal cells of the epithelium through a non-canonical endocytic pathway that involves the annexin A2/S100A10 heterotetramer (A2t). A2t is composed of two annexin A2 monomers bound to an S100A10 dimer and this interaction is a potential target to block HPV16 infection. Here, recently identified small molecule inhibitors of A2t (A2ti) were investigated for their ability to prevent HPV16 infection in vitro.

Methods

A2ti were added to HeLa cells in increasing concentrations prior to the addition of HPV16. Cytotoxicity was evaluated via trypan blue exclusion. HPV16 pseudovirion infection and fluorescently labelled HPV16 capsid internalization was measured with flow cytometry.

Results

A2ti blocked HPV16 infection by 100% without substantial cellular toxicity or reduction in cell growth. Furthermore, A2ti blocked HPV16 entry into epithelial cells by 65%, indicating that the observed inhibition of HPV16 infection is in part due to a block in entry and that non-infectious entry may occur in the absence of A2t binding.

Conclusions

These results demonstrate that targeting A2t may be an effective strategy to prevent HPV16 infection.

Keywords: HPV16; annexin A2/S100A10 heterotetramer; A2t

Journal Article.  1906 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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