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Viruses
Special Issues
Virus Receptors and Viral Tropism
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Virus Receptors and Viral Tropism

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 37600

Special Issue Editor

Dr. Petri Susi

E-Mail Website
Guest Editor
Institute of Biomedicine, University of Turku, Turku, Finland
Interests: enterovirus; rhinovirus; parechovirus; integrin; bioprocess; cell culture techniques; virus evolution; clinical virology; diagnostics; oncolytic virotherapy; antibody technologies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

One of the key characteristics of virus infection is viruses’ ability to recognize cell surface proteins, which mediate cellular entry and, therefore, initiate the replicative virus life cycle. Viral tropism occurs at both host and cell levels and determines the potential for infection and spreading between and within organisms. Slight alterations in viral structures may significantly affect the tropism and, hence, host pathogenesis of viruses, while interactions within cells define viruses´ ability to replicate and spread within tissues.

In this Special Issue of Viruses, we aim to discuss the recent discoveries regarding virus receptor-dependent and receptor-independent tropism. Specifically, we aim to address virus structure determination, virus sequencing, receptor identification, novel cell and tissue models for infectivity assays, entry steps, and viral genome evolution broadly affecting virus tropism. Findings dealing with drugs and vaccines with respect to virus evolution and tropism are also welcomed. I cordially invite you to contribute articles describing your most recent research findings and/or insights into this topic. We welcome original research articles, technical papers, and reviews.

Dr. Petri Susi
Guest Editor

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

  • entry
  • evolution
  • motif
  • receptor
  • structure
  • tropism

Published Papers (7 papers)

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Editorial

Jump to: Research, Review, Other

1 pages, 139 KiB  
Editorial
Special Issue: Virus Receptors and Viral Tropism
by Petri Susi
Viruses 2022, 14(1), 68; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010068 - 31 Dec 2021
Cited by 1 | Viewed by 1269
Abstract
Cell surface receptors play a key role in a virus’ ability to recognize and invade cells and tissues, which basically defines viral pathogenicity [...] Full article
(This article belongs to the Special Issue Virus Receptors and Viral Tropism)

Research

Jump to: Editorial, Review, Other

13 pages, 28331 KiB  
Article
Identification of RSV Fusion Protein Interaction Domains on the Virus Receptor, Nucleolin
by Peter Mastrangelo, Allysia A. Chin, Stephanie Tan, Amy H. Jeon, Cameron A. Ackerley, Karen K. Siu, Jeffrey E. Lee and Richard G. Hegele
Viruses 2021, 13(2), 261; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020261 - 08 Feb 2021
Cited by 22 | Viewed by 5221
Abstract
Nucleolin is an essential cellular receptor to human respiratory syncytial virus (RSV). Pharmacological targeting of the nucleolin RNA binding domain RBD1,2 can inhibit RSV infections in vitro and in vivo; however, the site(s) on RBD1,2 which interact with RSV are not known. We [...] Read more.
Nucleolin is an essential cellular receptor to human respiratory syncytial virus (RSV). Pharmacological targeting of the nucleolin RNA binding domain RBD1,2 can inhibit RSV infections in vitro and in vivo; however, the site(s) on RBD1,2 which interact with RSV are not known. We undertook a series of experiments designed to: document RSV-nucleolin co-localization on the surface of polarized MDCK cells using immunogold electron microscopy, to identify domains on nucleolin that physically interact with RSV using biochemical methods and determine their biological effects on RSV infection in vitro, and to carry out structural analysis toward informing future RSV drug development. Results of immunogold transmission and scanning electron microscopy showed RSV-nucleolin co-localization on the cell surface, as would be expected for a viral receptor. RSV, through its fusion protein (RSV-F), physically interacts with RBD1,2 and these interactions can be competitively inhibited by treatment with Palivizumab or recombinant RBD1,2. Treatment with synthetic peptides derived from two 12-mer domains of RBD1,2 inhibited RSV infection in vitro, with structural analysis suggesting these domains are potentially feasible for targeting in drug development. In conclusion, the identification and characterization of domains of nucleolin that interact with RSV provide the essential groundwork toward informing design of novel nucleolin-targeting compounds in RSV drug development. Full article
(This article belongs to the Special Issue Virus Receptors and Viral Tropism)
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12 pages, 2735 KiB  
Article
The Cell Tropism of Porcine Respiratory Coronavirus for Airway Epithelial Cells Is Determined by the Expression of Porcine Aminopeptidase N
by Ju-Yi Peng, Darsaniya Punyadarsaniya, Dai-Lun Shin, Suvarin Pavasutthipaisit, Andreas Beineke, Guangxing Li, Nai-Huei Wu and Georg Herrler
Viruses 2020, 12(11), 1211; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111211 - 23 Oct 2020
Cited by 10 | Viewed by 2659
Abstract
Porcine respiratory coronavirus (PRCoV) infects the epithelial cells in the respiratory tract of pigs, causing a mild respiratory disease. We applied air–liquid interface (ALI) cultures of well-differentiated porcine airway cells to mimic the respiratory tract epithelium in vitro and use it for analyzing [...] Read more.
Porcine respiratory coronavirus (PRCoV) infects the epithelial cells in the respiratory tract of pigs, causing a mild respiratory disease. We applied air–liquid interface (ALI) cultures of well-differentiated porcine airway cells to mimic the respiratory tract epithelium in vitro and use it for analyzing the infection by PRCoV. As reported for most coronaviruses, virus entry and virus release occurred mainly via the apical membrane domain. A novel finding was that PRCoV preferentially targets non-ciliated and among them the non-mucus-producing cells. Aminopeptidase N (APN), the cellular receptor for PRCoV was also more abundantly expressed on this type of cell suggesting that APN is a determinant of the cell tropism. Interestingly, differentiation-dependent differences were found both in the expression of pAPN and the susceptibility to PRCoV infection. Cells in an early differentiation stage express higher levels of pAPN and are more susceptible to infection by PRCoV than are well-differentiated cells. A difference in the susceptibility to infection was also detected when tracheal and bronchial cells were compared. The increased susceptibility to infection of bronchial epithelial cells was, however, not due to an increased abundance of APN on the cell surface. Our data reveal a complex pattern of infection in porcine differentiated airway epithelial cells that could not be elucidated with immortalized cell lines. The results are expected to have relevance also for the analysis of other respiratory viruses. Full article
(This article belongs to the Special Issue Virus Receptors and Viral Tropism)
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10 pages, 3839 KiB  
Communication
The Sialoside-Binding Pocket of SARS-CoV-2 Spike Glycoprotein Structurally Resembles MERS-CoV
by Mayanka Awasthi, Sahil Gulati, Debi P. Sarkar, Swasti Tiwari, Suneel Kateriya, Peeyush Ranjan and Santosh Kumar Verma
Viruses 2020, 12(9), 909; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090909 - 19 Aug 2020
Cited by 48 | Viewed by 9328
Abstract
COVID-19 novel coronavirus (CoV) disease caused by severe acquired respiratory syndrome (SARS)-CoV-2 manifests severe lethal respiratory illness in humans and has recently developed into a worldwide pandemic. The lack of effective treatment strategy and vaccines against the SARS-CoV-2 poses a threat to human [...] Read more.
COVID-19 novel coronavirus (CoV) disease caused by severe acquired respiratory syndrome (SARS)-CoV-2 manifests severe lethal respiratory illness in humans and has recently developed into a worldwide pandemic. The lack of effective treatment strategy and vaccines against the SARS-CoV-2 poses a threat to human health. An extremely high infection rate and multi-organ secondary infection within a short period of time makes this virus more deadly and challenging for therapeutic interventions. Despite high sequence similarity and utilization of common host-cell receptor, human angiotensin-converting enzyme-2 (ACE2) for virus entry, SARS-CoV-2 is much more infectious than SARS-CoV. Structure-based sequence comparison of the N-terminal domain (NTD) of the spike protein of Middle East respiratory syndrome (MERS)-CoV, SARS-CoV, and SARS-CoV-2 illustrate three divergent loop regions in SARS-CoV-2, which is reminiscent of MERS-CoV sialoside binding pockets. Comparative binding analysis with host sialosides revealed conformational flexibility of SARS-CoV-2 divergent loop regions to accommodate diverse glycan-rich sialosides. These key differences with SARS-CoV and similarity with MERS-CoV suggest an evolutionary adaptation of SARS-CoV-2 spike glycoprotein reciprocal interaction with host surface sialosides to infect host cells with wide tissue tropism. Full article
(This article belongs to the Special Issue Virus Receptors and Viral Tropism)
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Review

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21 pages, 993 KiB  
Review
Sialic Acid Receptors: The Key to Solving the Enigma of Zoonotic Virus Spillover
by Suresh V Kuchipudi, Rahul K Nelli, Abhinay Gontu, Rashmi Satyakumar, Meera Surendran Nair and Murugan Subbiah
Viruses 2021, 13(2), 262; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020262 - 08 Feb 2021
Cited by 41 | Viewed by 9562
Abstract
Emerging viral diseases are a major threat to global health, and nearly two-thirds of emerging human infectious diseases are zoonotic. Most of the human epidemics and pandemics were caused by the spillover of viruses from wild mammals. Viruses that infect humans and a [...] Read more.
Emerging viral diseases are a major threat to global health, and nearly two-thirds of emerging human infectious diseases are zoonotic. Most of the human epidemics and pandemics were caused by the spillover of viruses from wild mammals. Viruses that infect humans and a wide range of animals have historically caused devastating epidemics and pandemics. An in-depth understanding of the mechanisms of viral emergence and zoonotic spillover is still lacking. Receptors are major determinants of host susceptibility to viruses. Animal species sharing host cell receptors that support the binding of multiple viruses can play a key role in virus spillover and the emergence of novel viruses and their variants. Sialic acids (SAs), which are linked to glycoproteins and ganglioside serve as receptors for several human and animal viruses. In particular, influenza and coronaviruses, which represent two of the most important zoonotic threats, use SAs as cellular entry receptors. This is a comprehensive review of our current knowledge of SA receptor distribution among animal species and the range of viruses that use SAs as receptors. SA receptor tropism and the predicted natural susceptibility to viruses can inform targeted surveillance of domestic and wild animals to prevent the future emergence of zoonotic viruses. Full article
(This article belongs to the Special Issue Virus Receptors and Viral Tropism)
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11 pages, 283 KiB  
Review
Cellular Receptors Involved in KSHV Infection
by Emma van der Meulen, Meg Anderton, Melissa J. Blumenthal and Georgia Schäfer
Viruses 2021, 13(1), 118; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010118 - 17 Jan 2021
Cited by 10 | Viewed by 3417
Abstract
The process of Kaposi’s Sarcoma Herpes Virus’ (KSHV) entry into target cells is complex and engages several viral glycoproteins which bind to a large range of host cell surface molecules. Receptors for KSHV include heparan sulphate proteoglycans (HSPGs), several integrins and Eph receptors, [...] Read more.
The process of Kaposi’s Sarcoma Herpes Virus’ (KSHV) entry into target cells is complex and engages several viral glycoproteins which bind to a large range of host cell surface molecules. Receptors for KSHV include heparan sulphate proteoglycans (HSPGs), several integrins and Eph receptors, cystine/glutamate antiporter (xCT) and Dendritic Cell-Specific Intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). This diverse range of potential binding and entry sites allows KSHV to have a broad cell tropism, and entry into specific cells is dependent on the available receptor repertoire. Several molecules involved in KSHV entry have been well characterized, particularly those postulated to be associated with KSHV-associated pathologies such as Kaposi’s Sarcoma (KS). In this review, KSHV infection of specific cell types pertinent to its pathogenesis will be comprehensively summarized with a focus on the specific cell surface binding and entry receptors KSHV exploits to gain access to a variety of cell types. Gaps in the current literature regarding understanding interactions between KSHV glycoproteins and cellular receptors in virus infection are identified which will lead to the development of virus infection intervention strategies. Full article
(This article belongs to the Special Issue Virus Receptors and Viral Tropism)

Other

8 pages, 1042 KiB  
Brief Report
Comparative Study of SARS-CoV-2, SARS-CoV-1, MERS-CoV, HCoV-229E and Influenza Host Gene Expression in Asthma: Importance of Sex, Disease Severity, and Epithelial Heterogeneity
by Mackenzie E. Coden, Lucas F. Loffredo, Hiam Abdala-Valencia and Sergejs Berdnikovs
Viruses 2021, 13(6), 1081; https://0-doi-org.brum.beds.ac.uk/10.3390/v13061081 - 05 Jun 2021
Cited by 8 | Viewed by 3106
Abstract
Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate, and severe asthmatics, we characterized the [...] Read more.
Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate, and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location, and disease endotype. We found sexual dimorphism in the expression of SARS-CoV-2-related genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2, and TMPRSS4, were highly upregulated in both sexes. Overall, changes in SARS-CoV-2-related gene expression were specific to the Th2 high molecular endotype of asthma and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors wascorrelated with loss of club and ciliated cells in Th2 high asthma. Meanwhile, the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) was associated with increased goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype, and changes in epithelial heterogeneity as potential factors underlying asthmatic susceptibility, or lack thereof, to SARS-CoV-2. Full article
(This article belongs to the Special Issue Virus Receptors and Viral Tropism)
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