Authors:	Fast, Laura Mikuličić, Snježana Fritzen, Anna Schwickert, Jonas Boukhallouk, Fatima Hochdorfer, Daniel Sinzger, Christian Suarez, Henar Monk, Peter Yáñez-Mó, María Lieber, Diana Florin, Luise
Title:	Inhibition of tetraspanin functions impairs human papillomavirus and cytomegalovirus infections
Online publication date:	19-Dec-2018
Year of first publication:	2018
Language:	english
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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-258
URN:	urn:nbn:de:hebis:77-publ-587143
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International journal of molecular sciences 19 10
Pages or article number:	Art. 3007
Publisher:	Molecular Diversity Preservation International
Publisher place:	Basel
Issue date:	2018
ISSN:	1422-0067 1661-6596
Publisher URL:	http://dx.doi.org/10.3390/ijms19103007
Publisher DOI:	10.3390/ijms19103007
Appears in collections:	JGU-Publikationen