Inhibition of tetraspanin functions impairs human papillomavirus and cytomegalovirus infections
peer-reviewed
Erstveröffentlichung
2018-10-02Authors
Fast, Laura A.
Mikuličić, Snježana
Fritzen, Anna
Schwickert, Jonas
Boukhallouk, Fatima
Wissenschaftlicher Artikel
Published in
International Journal of Molecular Sciences ; 19 (2018), 10. - Art.-Nr. 3007. - eISSN 1422-0067
Link to original publication
https://dx.doi.org/10.3390/ijms19103007Institutions
UKU. Institut für VirologieDocument version
published version (publisher's PDF)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
Subject headings
[GND]: Humanes Papillomavirus | Cytomegalie-Virus[MeSH]: Human papillomavirus viruses | Cytomegalovirus | Tetraspanins | Virus internalization
[Free subject headings]: human papillomavirus | HPV16 | human cytomegalovirus | tetraspanin | virus entry | blocking peptide | IC 50
[DDC subject group]: DDC 610 / Medicine & health
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Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-47809
Fast, Laura A. et al. (2023): Inhibition of tetraspanin functions impairs human papillomavirus and cytomegalovirus infections. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-47809
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