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Viruses
Special Issues
TMPRSS2 in Influenza Virus and Coronavirus Infections
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TMPRSS2 in Influenza Virus and Coronavirus Infections

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 1633

Special Issue Editors

Prof. Dr. Judy Wai Ping Yam

E-Mail Website
Guest Editor
Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Interests: hepatocellular carcinoma; extracellular vesicles; tumor microenvironment
Dr. Sze Keong Tey

E-Mail Website
Guest Editor
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Interests: TMPRSS2; SARS-CoV-2; extracellular vesicles; tumor microenvironment; cancer metastasis; tumor biology

Special Issue Information

Dear Colleagues,

Since the early 21st century, epidemics or pandemics of influenza virus and coronavirus, both of which are highly contagious viral pathogens, have occurred and imposed a significant impact on global healthcare systems. Indeed, the co-infection of SARS-CoV-2, the most recently discovered coronavirus that is responsible for the COVID-19 pandemic, with influenza viruses and even other respiratory pathogens has been reported, which may cause an even more significant threat to humankind. Emerging evidence has supported the unequivocal role of TMPRSS2 in influenza virus and coronavirus infections. Although the physiological role remains largely elusive, TMPRSS2 serves as a major player in SARS-CoV-2 entry as well as priming glycoproteins of other respiratory viruses. Therefore, targeting TMPRSS2 has been proposed as a promising anti-viral approach. The aim of this Special Issue is to highlight the latest studies on the role of TMPRSS2 in influenza virus and coronavirus infections, providing great insight into the mechanistic pathway, transmission and epidemiology.

We welcome the submission of original research, brief research reports, reviews and communication articles that address these issues.

Prof. Dr. Judy Wai Ping Yam
Dr. Sze Keong Tey
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • TMPRSS2
  • influenza virus
  • coronavirus
  • viral infection
  • treatment of viral diseases

Published Papers (1 paper)

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Research

16 pages, 6480 KiB  
Article
The Transmembrane Protease Serine 2 (TMPRSS2) Non-Protease Domains Regulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike-Mediated Virus Entry
by Romano Strobelt, Julia Adler and Yosef Shaul
Viruses 2023, 15(10), 2124; https://doi.org/10.3390/v15102124 - 19 Oct 2023
Viewed by 1303
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells by binding to the angiotensin-converting enzyme 2 (hACE2) receptor. This process is aided by the transmembrane protease serine 2 (TMPRSS2), which enhances entry efficiency and infectiousness by cleaving the SARS-CoV-2 surface glycoprotein (Spike). [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells by binding to the angiotensin-converting enzyme 2 (hACE2) receptor. This process is aided by the transmembrane protease serine 2 (TMPRSS2), which enhances entry efficiency and infectiousness by cleaving the SARS-CoV-2 surface glycoprotein (Spike). The cleavage primes the Spike protein, promoting membrane fusion instead of receptor-mediated endocytosis. Despite the pivotal role played by TMPRSS2, our understanding of its non-protease distinct domains remains limited. In this report, we present evidence indicating the potential phosphorylation of a minimum of six tyrosine residues within the cytosolic tail (CT) of TMPRSS2. Via the use of TMPRSS2 CT phospho-mimetic mutants, we observed a reduction in TMPRSS2 protease activity, accompanied by a decrease in SARS-CoV-2 pseudovirus transduction, which was found to occur mainly via the endosomal pathway. We expanded our investigation beyond TMPRSS2 CT and discovered the involvement of other non-protease domains in regulating infection. Our co-immunoprecipitation experiments demonstrated a strong interaction between TMPRSS2 and Spike. We revealed a 21 amino acid long TMPRSS2-Spike-binding region (TSBR) within the TMPRSS2 scavenger receptor cysteine-rich (SRCR) domain that contributes to this interaction. Our study sheds light on novel functionalities associated with TMPRSS2’s cytosolic tail and SRCR region. Both of these regions have the capability to regulate SARS-CoV-2 entry pathways. These findings contribute to a deeper understanding of the complex interplay between viral entry and host factors, opening new avenues for potential therapeutic interventions. Full article
(This article belongs to the Special Issue TMPRSS2 in Influenza Virus and Coronavirus Infections)
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