التفاصيل البيبلوغرافية
| العنوان: |
The US21 viroporin of human cytomegalovirus stimulates cell migration and adhesion |
| المؤلفون: |
Luganini, Anna, Serra, Valentina, Scarpellino, Giorgia, Bhat, Shree Madhu, Munaron, Luca, Fiorio Pla, Alessandra, Gribaudo, Giorgio |
| المساهمون: |
Shenk, Thomas, Regione Piemonte, Ministero dell'Istruzione, dell'Università e della Ricerca |
| المصدر: |
mBio ; ISSN 2150-7511 |
| بيانات النشر: |
American Society for Microbiology |
| سنة النشر: |
2023 |
| الوصف: |
The human cytomegalovirus (HCMV) US12 gene family contributes to virus-host interactions by regulating the virus’ cell tropism and its evasion of host innate immune responses. US21, one of the 10 US12 genes (US12–US21), is a descendant of a captured cellular transmembrane BAX inhibitor motif-containing gene. It encodes a 7TMD endoplasmic reticulum (ER)-resident viroporin (pUS21) capable of reducing the Ca 2+ content of ER stores, which, in turn, protects cells against apoptosis. Since regulation of Ca 2+ homeostasis affects a broad range of cellular responses, including cell motility, we investigated whether pUS21 might also interfere with this cytobiological consequence of Ca 2+ signaling. Indeed, deletion of the US21 gene impaired the ability of HCMV-infected cells to migrate, whereas expression of US21 protein stimulated cell migration and adhesion, as well as focal adhesion (FA) dynamics, in a way that depended on its ability to manipulate ER Ca 2+ content. Mechanistic studies revealed pUS21-mediated cell migration to involve calpain 2 activation since its inhibition prevented the viroporin’s effects on cell motility. Pertinently, pUS21 expression stimulated a store-operated Ca 2+ entry (SOCE) mechanism that may determine the activation of calpain 2 by promoting Ca 2+ entry. Furthermore, pUS21 was observed to interact with talin-1, a calpain 2 substrate, and crucial protein component of FA complexes. A functional consequence of this interaction was confirmed by talin-1 knockdown, which abrogated the pUS21-mediated increase in cell migration. Together, these results indicate the US21-encoded viroporin to be a viral regulator of cell adhesion and migration in the context of HCMV infection. IMPORTANCE Human cytomegalovirus (HCMV) is an opportunistic pathogen that owes part of its success to the capture, duplication, and tuning of cellular genes to generate modern viral proteins which promote infection and persistence in the host by interfering with many cell biochemical and physiological pathways. The ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1128/mbio.00749-23 |
| الإتاحة: |
https://doi.org/10.1128/mbio.00749-23Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ ; https://journals.asm.org/non-commercial-tdm-licenseTest |
| رقم الانضمام: |
edsbas.2B6E9407 |
| قاعدة البيانات: |
BASE |
