1887

Journal of General Virology header logo

Volume 97, Issue 2

Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection Free

Abstract

Herpes simplex virus (HSV) was originally implicated in the aetiology of cervical cancer, and although high-risk human papillomavirus (HPV) is now the accepted causative agent, the epidemiological link between HSV and HPV-associated cancers persists. The annexin A2 heterotetramer (A2t) has been shown to mediate infectious HPV type 16 (HPV16) uptake by human keratinocytes, and secretory leukocyte protease inhibitor (SLPI), an endogenous A2t ligand, inhibits HPV16 uptake and infection. Interestingly, HSV infection induces a sustained downregulation of SLPI in epithelial cells, which we hypothesized promotes HPV16 infection through A2t. Here, we show that infection of human keratinocytes with HSV-1 or HSV-2, but not with an HSV-1 ICP4 deletion mutant that does not downregulate SLPI, leads to a >70 % reduction of SLPI mRNA and a >60 % decrease in secreted SLPI protein. Consequently, we observed a significant increase in the uptake of HPV16 virus-like particles and gene transduction by HPV16 pseudovirions (two- and 2.5-fold, respectively) in HSV-1- and HSV-2-infected human keratinocyte cell cultures compared with uninfected cells, whereas exogenously added SLPI reversed this effect. Using a SiMPull (single-molecule pulldown) assay, we demonstrated that endogenously secreted SLPI interacts with A2t on epithelial cells in an autocrine/paracrine manner. These results suggested that ongoing HSV infection and resultant downregulation of local levels of SLPI may impart a greater susceptibility for keratinocytes to HPV16 infection through the host cell receptor A2t, providing a mechanism that may, in part, provide an explanation for the aetiological link between HSV and HPV-associated cancers.

  • Received:
  • Accepted:
  • Published Online:
© 2015 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000341
2016-02-01
2024-04-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/2/422.html?itemId=/content/journal/jgv/10.1099/jgv.0.000341&mimeType=html&fmt=ahah

References

  1. Abaitua F., Zia F. R., Hollinshead M., O'Hare P. 2013; Polarized cell migration during cell-to-cell transmission of herpes simplex virus in human skin keratinocytes. J Virol 87:7921–7932 [View Article][PubMed]
     [Google Scholar]
  2. Alexopoulou A. N., Multhaupt H. A., Couchman J. R. 2007; Syndecans in wound healing, inflammation and vascular biology. Int J Biochem Cell Biol 39:505–528 [View Article][PubMed]
     [Google Scholar]
  3. Bacsa S., Karasneh G., Dosa S., Liu J., Valyi-Nagy T., Shukla D. 2011; Syndecan-1 and syndecan-2 play key roles in herpes simplex virus type-1 infection. J Gen Virol 92:733–743 [View Article][PubMed]
     [Google Scholar]
  4. Blaho J. A., Morton E. R., Yedowitz J. C. 2005; Herpes simplex virus: propagation, quantification, and storage. Curr Protoc Microbiol 14:11–123
     [Google Scholar]
  5. Bosch F. X., Manos M. M., Muñoz N., Sherman M., Jansen A. M., Peto J., Schiffman M. H., Moreno V., Kurman R., Shah K. V. 1995; Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87:796–802 [View Article][PubMed]
     [Google Scholar]
  6. Boukamp P., Petrussevska R. T., Breitkreutz D., Hornung J., Markham A., Fusenig N. E. 1988; Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106:761–771 [View Article][PubMed]
     [Google Scholar]
  7. Buck C. B., Thompson C. D. 2007; Production of papillomavirus-based gene transfer vectors. Curr Protoc Cell Biol 26:11–119
     [Google Scholar]
  8. Chaturvedi A. K., Engels E. A., Pfeiffer R. M., Hernandez B. Y., Xiao W., Kim E., Jiang B., Goodman M. T., Sibug-Saber M., other authors. 2011; Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29:4294–4301 [View Article][PubMed]
     [Google Scholar]
  9. Chen R., Aaltonen L. M., Vaheri A. 2005; Human papillomavirus type 16 in head and neck carcinogenesis. Rev Med Virol 15:351–363 [View Article][PubMed]
     [Google Scholar]
  10. Cordes C., Häsler R., Werner C., Görögh T., Röcken C., Hebebrand L., Kast W. M., Hoffmann M., Schreiber S., Ambrosch P. 2011; The level of secretory leukocyte protease inhibitor is decreased in metastatic head and neck squamous cell carcinoma. Int J Oncol 39:185–191[PubMed]
     [Google Scholar]
  11. Drannik A. G., Henrick B. M., Rosenthal K. L. 2011; War and peace between WAP and HIV: role of SLPI, trappin-2, elafin and ps20 in susceptibility to HIV infection. Biochem Soc Trans 39:1427–1432 [View Article][PubMed]
     [Google Scholar]
  12. Dziduszko A., Ozbun M. A. 2013; Annexin A2 and S100A10 regulate human papillomavirus type 16 entry and intracellular trafficking in human keratinocytes. J Virol 87:7502–7515 [View Article][PubMed]
     [Google Scholar]
  13. Fakioglu E., Wilson S. S., Mesquita P. M., Hazrati E., Cheshenko N., Blaho J. A., Herold B. C. 2008; Herpes simplex virus downregulates secretory leukocyte protease inhibitor: a novel immune evasion mechanism. J Virol 82:9337–9344 [View Article][PubMed]
     [Google Scholar]
  14. Hammarstedt L., Lindquist D., Dahlstrand H., Romanitan M., Dahlgren L. O., Joneberg J., Creson N., Lindholm J., Ye W., other authors. 2006; Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer 119:2620–2623 [View Article][PubMed]
     [Google Scholar]
  15. Hoffmann M., Quabius E. S., Tribius S., Hebebrand L., Görögh T., Halec G., Kahn T., Hedderich J., Röcken C., other authors. 2013; Human papillomavirus infection in head and neck cancer: the role of the secretory leukocyte protease inhibitor. Oncol Rep 29:1962–1968[PubMed]
     [Google Scholar]
  16. Huang H. S., Lambert P. F. 2012; Use of an in vivo animal model for assessing the role of integrin α6β4 and syndecan-1 in early steps in papillomavirus infection. Virology 433:395–400 [View Article][PubMed]
     [Google Scholar]
  17. Jain A., Liu R., Xiang Y. K., Ha T. 2012; Single-molecule pull-down for studying protein interactions. Nat Protoc 7:445–452 [View Article][PubMed]
     [Google Scholar]
  18. Kawana Y., Kawana K., Yoshikawa H., Taketani Y., Yoshiike K., Kanda T. 2001; Human papillomavirus type 16 minor capsid protein L2 N-terminal region containing a common neutralization epitope binds to the cell surface and enters the cytoplasm. J Virol 75:2331–2336 [View Article][PubMed]
     [Google Scholar]
  19. Kirnbauer R., Booy F., Cheng N., Lowy D. R., Schiller J. T. 1992; Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci U S A 89:12180–12184 [View Article][PubMed]
     [Google Scholar]
  20. Kramps J. A., Franken C., Dijkman J. H. 1984; ELISA for quantitative measurement of low-molecular-weight bronchial protease inhibitor in human sputum. Am Rev Respir Dis 129:959–963[PubMed]
     [Google Scholar]
  21. Kreimer A. R., Clifford G. M., Boyle P., Franceschi S. 2005; Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14:467–475 [View Article][PubMed]
     [Google Scholar]
  22. Ma G., Greenwell-Wild T., Lei K., Jin W., Swisher J., Hardegen N., Wild C. T., Wahl S. M. 2004; Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection. J Exp Med 200:1337–1346 [View Article][PubMed]
     [Google Scholar]
  23. Marconi P., Krisky D., Oligino T., Poliani P. L., Ramakrishnan R., Goins W. F., Fink D. J., Glorioso J. C. 1996; Replication-defective herpes simplex virus vectors for gene transfer in vivo . Proc Natl Acad Sci U S A 93:11319–11320 [View Article][PubMed]
     [Google Scholar]
  24. Mehanna H., Beech T., Nicholson T., El-Hariry I., McConkey C., Paleri V., Roberts S. 2013; Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer – systematic review and meta-analysis of trends by time and region. Head Neck 35:747–755 [View Article][PubMed]
     [Google Scholar]
  25. Moody C. A., Laimins L. A. 2010; Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 10:550–560 [View Article][PubMed]
     [Google Scholar]
  26. Paba P., Bonifacio D., Di Bonito L., Ombres D., Favalli C., Syrjänen K., Ciotti M. 2008; Co-expression of HSV2 and Chlamydia trachomatis in HPV-positive cervical cancer and cervical intraepithelial neoplasia lesions is associated with aberrations in key intracellular pathways. Intervirology 51:230–234 [View Article][PubMed]
     [Google Scholar]
  27. Raff A. B., Woodham A. W., Raff L. M., Skeate J. G., Yan L., Da Silva D. M., Schelhaas M., Kast W. M. 2013; The evolving field of human papillomavirus receptor research: a review of binding and entry. J Virol 87:6062–6072 [View Article][PubMed]
     [Google Scholar]
  28. Ragin C. C., Taioli E. 2007; Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121:1813–1820 [View Article][PubMed]
     [Google Scholar]
  29. Schillinger J. A., McKinney C. M., Garg R., Gwynn R. C., White K., Lee F., Blank S., Thorpe L., Frieden T. 2008; Seroprevalence of herpes simplex virus type 2 and characteristics associated with undiagnosed infection: New York City, 2004. Sex Transm Dis 35:599–606 [View Article][PubMed]
     [Google Scholar]
  30. Shafti-Keramat S., Handisurya A., Kriehuber E., Meneguzzi G., Slupetzky K., Kirnbauer R. 2003; Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses. J Virol 77:13125–13135 [View Article][PubMed]
     [Google Scholar]
  31. Shillitoe E. J., Silverman S. Jr 1979; Oral cancer and herpes simplex virus – a review. Oral Surg Oral Med Oral Pathol 48:216–224 [View Article][PubMed]
     [Google Scholar]
  32. Smith J. W., Torres J. E., Holmquist N. D. 1979; Association of Herpes simplex virus (HSV) with cervical cancer by lymphocyte reactivity with HSV-1 and HSV-2 antigens. Am J Epidemiol 110:141–147[PubMed]
     [Google Scholar]
  33. Smith J. S., Herrero R., Bosetti C., Muñoz N., Bosch F. X., Eluf-Neto J., Castellsagué X., Meijer C. J., Van den Brule A. J., other authors. 2002; Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst 94:1604–1613 [View Article][PubMed]
     [Google Scholar]
  34. Spear P. G. 2004; Herpes simplex virus: receptors and ligands for cell entry. Cell Microbiol 6:401–410 [View Article][PubMed]
     [Google Scholar]
  35. Starr J. R., Daling J. R., Fitzgibbons E. D., Madeleine M. M., Ashley R., Galloway D. A., Schwartz S. M. 2001; Serologic evidence of herpes simplex virus 1 infection and oropharyngeal cancer risk. Cancer Res 61:8459–8464[PubMed]
     [Google Scholar]
  36. Stokley S., Jeyarajah J., Yankey D., Cano M., Gee J., Roark J., Curtis R. C., Markowitz L., Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC & Centers for Disease Control and Prevention (CDC). 2014; Human papillomavirus vaccination coverage among adolescents, 2007–2013, and postlicensure vaccine safety monitoring, 2006–2014 – United States. MMWR Morb Mortal Wkly Rep 63:620–624[PubMed]
     [Google Scholar]
  37. Surviladze Z., Dziduszko A., Ozbun M. A. 2012; Essential roles for soluble virion-associated heparan sulfonated proteoglycans and growth factors in human papillomavirus infections. PLoS Pathog 8:e1002519 [View Article][PubMed]
     [Google Scholar]
  38. Vogelmeier C., Hubbard R. C., Fells G. A., Schnebli H. P., Thompson R. C., Fritz H., Crystal R. G. 1991; Anti-neutrophil elastase defense of the normal human respiratory epithelial surface provided by the secretory leukoprotease inhibitor. J Clin Invest 87:482–488 [View Article][PubMed]
     [Google Scholar]
  39. Woodham A. W., Da Silva D. M., Skeate J. G., Raff A. B., Ambroso M. R., Brand H. E., Isas J. M., Langen R., Kast W. M. 2012; The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection. PLoS One 7:e43519 [View Article][PubMed]
     [Google Scholar]
  40. Woodham A. W., Raff A. B., Raff L. M., Da Silva D. M., Yan L., Skeate J. G., Wong M. K., Lin Y. G., Kast W. M. 2014; Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression. J Immunol 192:4748–4757 [View Article][PubMed]
     [Google Scholar]
  41. Woodham A. W., Taylor J. R., Jimenez A. I., Skeate J. G., Schmidt T., Brand H. E., Da Silva D. M., Kast W. M. 2015; Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection. J Antimicrob Chemother 70:1686–1690[PubMed]
     [Google Scholar]
  42. Zhao Y., Cao X., Zheng Y., Tang J., Cai W., Wang H., Gao Y., Wang Y. 2012; Relationship between cervical disease and infection with human papillomavirus types 16 and 18, and herpes simplex virus 1 and 2. J Med Virol 84:1920–1927 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000341
Loading
Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection
J. Gen. Virol. 97, 422 (2016); https://doi.org/10.1099/jgv.0.000341
/content/journal/jgv/10.1099/jgv.0.000341
/content/journal/jgv/10.1099/jgv.0.000341
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error