Next Article in Journal
Rice Routes of Countering Xanthomonas oryzae
Next Article in Special Issue
HPV16-Related Cervical Cancers and Precancers Have Increased Levels of Host Cell DNA Methylation in Women Living with HIV
Previous Article in Journal
Comparison on Photosynthesis and Antioxidant Defense Systems in Wheat with Different Ploidy Levels and Octoploid Triticale
Previous Article in Special Issue
ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 19
Issue 10
10.3390/ijms19103007
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Inhibition of Tetraspanin Functions Impairs Human Papillomavirus and Cytomegalovirus Infections

by
Laura A. Fast
1,†,
Snježana Mikuličić
1,†,
Anna Fritzen
1,
Jonas Schwickert
1,
Fatima Boukhallouk
2,
Daniel Hochdorfer
3,
Christian Sinzger
3,
Henar Suarez
4,5,
Peter N. Monk
6,
María Yáñez-Mó
4,5,
Diana Lieber
3 and
Luise Florin
1,*
1
Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55122 Mainz, Germany
2
Institute for Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg University, 55122 Mainz, Germany
3
Institute of Virology, Ulm University Medical Center, 89081 Ulm, Germany
4
Departamento de Biología Molecular, UAM, 28049 Madrid, Spain
5
Centro de Biología Molecular Severo Ochoa (CBM-SO), Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain
6
Department of Infection, Immunity and Cardiovascular Disease, School of Medicine and Biomedical Science, University of Sheffield, Sheffield S10 2RX, England, UK
*
Author to whom correspondence should be addressed.
†
L.A.F. and S.M. contributed equally to the manuscript.
Int. J. Mol. Sci. 2018, 19(10), 3007; https://doi.org/10.3390/ijms19103007
Submission received: 4 September 2018 / Revised: 23 September 2018 / Accepted: 27 September 2018 / Published: 2 October 2018
(This article belongs to the Special Issue Molecular Research on Cervical Cancer)
Browse Figures
Versions Notes

Abstract

Tetraspanins are suggested to regulate the composition of cell membrane components and control intracellular transport, which leaves them vulnerable to utilization by pathogens such as human papillomaviruses (HPV) and cytomegaloviruses (HCMV) to facilitate host cell entry and subsequent infection. In this study, by means of cellular depletion, the cluster of differentiation (CD) tetraspanins CD9, CD63, and CD151 were found to reduce HPV16 infection in HeLa cells by 50 to 80%. Moreover, we tested recombinant proteins or peptides of specific tetraspanin domains on their effect on the most oncogenic HPV type, HPV16, and HCMV. We found that the C-terminal tails of CD63 and CD151 significantly inhibited infections of both HPV16 and HCMV. Although CD9 was newly identified as a key cellular factor for HPV16 infection, the recombinant CD9 C-terminal peptide had no effect on infection. Based on the determined half-maximal inhibitory concentration (IC50), we classified CD63 and CD151 C-terminal peptides as moderate to potent inhibitors of HPV16 infection in HeLa and HaCaT cells, and in EA.hy926, HFF (human foreskin fibroblast) cells, and HEC-LTT (human endothelial cell-large T antigen and telomerase) cells for HCMV, respectively. These results indicate that HPV16 and HCMV share similar cellular requirements for their entry into host cells and reveal the necessity of the cytoplasmic CD151 and CD63 C-termini in virus infections. Furthermore, this highlights the suitability of these peptides for functional investigation of tetraspanin domains and as inhibitors of pathogen infections.
Keywords: human papillomavirus; HPV16; human cytomegalovirus; tetraspanin; virus entry; blocking peptide; IC50 human papillomavirus; HPV16; human cytomegalovirus; tetraspanin; virus entry; blocking peptide; IC50
Graphical Abstract

Share and Cite

MDPI and ACS Style

Fast, L.A.; Mikuličić, S.; Fritzen, A.; Schwickert, J.; Boukhallouk, F.; Hochdorfer, D.; Sinzger, C.; Suarez, H.; Monk, P.N.; Yáñez-Mó, M.; et al. Inhibition of Tetraspanin Functions Impairs Human Papillomavirus and Cytomegalovirus Infections. Int. J. Mol. Sci. 2018, 19, 3007. https://doi.org/10.3390/ijms19103007

AMA Style

Fast LA, Mikuličić S, Fritzen A, Schwickert J, Boukhallouk F, Hochdorfer D, Sinzger C, Suarez H, Monk PN, Yáñez-Mó M, et al. Inhibition of Tetraspanin Functions Impairs Human Papillomavirus and Cytomegalovirus Infections. International Journal of Molecular Sciences. 2018; 19(10):3007. https://doi.org/10.3390/ijms19103007

Chicago/Turabian Style

Fast, Laura A., Snježana Mikuličić, Anna Fritzen, Jonas Schwickert, Fatima Boukhallouk, Daniel Hochdorfer, Christian Sinzger, Henar Suarez, Peter N. Monk, María Yáñez-Mó, and et al. 2018. "Inhibition of Tetraspanin Functions Impairs Human Papillomavirus and Cytomegalovirus Infections" International Journal of Molecular Sciences 19, no. 10: 3007. https://doi.org/10.3390/ijms19103007

APA Style

Fast, L. A., Mikuličić, S., Fritzen, A., Schwickert, J., Boukhallouk, F., Hochdorfer, D., Sinzger, C., Suarez, H., Monk, P. N., Yáñez-Mó, M., Lieber, D., & Florin, L. (2018). Inhibition of Tetraspanin Functions Impairs Human Papillomavirus and Cytomegalovirus Infections. International Journal of Molecular Sciences, 19(10), 3007. https://doi.org/10.3390/ijms19103007

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop