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The Roles of Growth Factors, Cytokines and Their Receptors in...
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The Roles of Growth Factors, Cytokines and Their Receptors in Viral Infections

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 11643

Special Issue Editors

Dr. Alexander David Barrow

E-Mail Website
Guest Editor
The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia
Interests: poxvirus; skin infection and repair; growth factors; cytokines; chemokines
Dr. Lyn Wise

E-Mail Website1 Website2
Guest Editor
Department of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand
Interests: poxvirus; skin infection and repair; growth factors; cytokines; chemokines

Special Issue Information

Dear Colleagues,

Growth factors, cytokines and their receptors are known to facilitate virus infection. Viruses can use the receptors to physically attach to the cell surface, with the ligand binding inducing virus internalisation, and the subsequent signaling supporting viral genome replication. As such, many viruses deploy strategies to enhance this process, with some inducing the expression of cellular growth factors and cytokines, while other viruses produce their own growth factors or cytokine homologues that they have acquired from their hosts. The pathogenic effects of excess growth factor and cytokine production can also extend beyond the infected cell; the subversion or promotion of host anti-viral and immune responses has been reported, as has the production of proliferative lesions that facilitate virus replication and dissemination or even promote cancer. Thus, therapeutics that target growth factors, cytokines or their receptor signalling pathways are being investigated for the treatment of established and emerging viral infections. Meanwhile, numerous virus-derived growth factors and cytokines are being explored as novel immunomodulatory and regenerative therapies.

In this Special Issue, we aim to assemble a collection of original research and review articles to provide a comprehensive overview of recent advancements made in the understanding of the multifaceted roles of growth factors, cytokines and their receptors in viral pathogenesis and immunity, as well as efforts to target them during virus infection or exploit the virus-derived versions as therapeutic strategies.

The potential topics include, but are not limited to, the following:

  • Recent evolutionary, genetic, biochemical, structural or biological reports on virus-encoded growth factors and cytokines
  • The roles of growth factors and/or cytokines and their receptors in the viral lifecycle, including entry, replication and dissemination
  • The roles of growth factors, cytokines and their receptors in the subversion of the immune response
  • Advancements in drugs targeting growth factors, cytokines or their receptors for the treatment of viral infections
  • Developments in the exploitation of virus-derived growth factors and cytokines as therapeutics:

Dr. Alexander David Barrow
Dr. Lyn Wise
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. Pathogens 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 2200 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

  • growth factors
  • cytokine
  • receptor
  • signalling
  • viral mimicry
  • viral pathogenesis
  • viral oncogenesis
  • viral immunity
  • virus lifecycle
  • virus entry
  • replication
  • dissemination
  • immune subversion
  • drugs
  • therapeutics

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (4 papers)

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18 pages, 8209 KiB  
Article
IL17RB and IL17REL Expression Are Associated with Improved Prognosis in HPV-Infected Head and Neck Squamous Cell Carcinomas
by Yuhan Sun, Md. Abdullah Al Kamran Khan, Stefano Mangiola and Alexander David Barrow
Pathogens 2023, 12(4), 572; https://doi.org/10.3390/pathogens12040572 - 7 Apr 2023
Cited by 1 | Viewed by 2124
Abstract
Changes in the cellular secretome are implicated in virus infection, malignancy, and anti-tumor immunity. We analyzed the association between transcriptional signatures (TS) from 24 different immune and stromal cell types on the prognosis of HPV-infected and HPV-free head and neck squamous carcinoma (HNSCC) [...] Read more.
Changes in the cellular secretome are implicated in virus infection, malignancy, and anti-tumor immunity. We analyzed the association between transcriptional signatures (TS) from 24 different immune and stromal cell types on the prognosis of HPV-infected and HPV-free head and neck squamous carcinoma (HNSCC) patients from The Cancer Genome Atlas (TCGA) cohort. We found that HPV-positive HNSCC patients have tumors with elevated immune cell TS and improved prognosis, which was specifically associated with an increased tumor abundance of memory B and activated natural killer (NK) cell TS, compared to HPV-free HNSCC patients. HPV-infected patients upregulated many transcripts encoding secreted factors, such as growth factors, hormones, chemokines and cytokines, and their cognate receptors. Analysis of secretome transcripts and cognate receptors revealed that tumor expression of IL17RB and IL17REL are associated with a higher viral load and memory B and activated NK cell TS, as well as improved prognosis in HPV-infected HNSCC patients. The transcriptional parameters that we describe may be optimized to improve prognosis and risk stratification in the clinic and provide insights into gene and cellular targets that may potentially enhance anti-tumor immunity mediated by NK cells and memory B cells in HPV-infected HNSCC patients. Full article
(This article belongs to the Special Issue The Roles of Growth Factors, Cytokines and Their Receptors in Viral Infections)
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20 pages, 6869 KiB  
Article
Virus-Derived Chemokine Modulating Protein Pre-Treatment Blocks Chemokine–Glycosaminoglycan Interactions and Significantly Reduces Transplant Immune Damage
by Isabela R. Zanetti, Michelle Burgin, Liqiang Zhang, Steve T. Yeh, Sriram Ambadapadi, Jacquelyn Kilbourne, Jordan R. Yaron, Kenneth M. Lowe, Juliane Daggett-Vondras, David Fonseca, Ryan Boyd, Dara Wakefield, William Clapp, Efrem Lim, Hao Chen and Alexandra Lucas
Pathogens 2022, 11(5), 588; https://doi.org/10.3390/pathogens11050588 - 16 May 2022
Cited by 2 | Viewed by 2400
Abstract
Immune cell invasion after the transplantation of solid organs is directed by chemokines binding to glycosaminoglycans (GAGs), creating gradients that guide immune cell infiltration. Renal transplant is the preferred treatment for end stage renal failure, but organ supply is limited and allografts are [...] Read more.
Immune cell invasion after the transplantation of solid organs is directed by chemokines binding to glycosaminoglycans (GAGs), creating gradients that guide immune cell infiltration. Renal transplant is the preferred treatment for end stage renal failure, but organ supply is limited and allografts are often injured during transport, surgery or by cytokine storm in deceased donors. While treatment for adaptive immune responses during rejection is excellent, treatment for early inflammatory damage is less effective. Viruses have developed highly active chemokine inhibitors as a means to evade host responses. The myxoma virus-derived M-T7 protein blocks chemokine: GAG binding. We have investigated M-T7 and also antisense (ASO) as pre-treatments to modify chemokine: GAG interactions to reduce donor organ damage. Immediate pre-treatment of donor kidneys with M-T7 to block chemokine: GAG binding significantly reduced the inflammation and scarring in subcapsular and subcutaneous allografts. Antisense to N-deacetylase N-sulfotransferase1 (ASONdst1) that modifies heparan sulfate, was less effective with immediate pre-treatment, but reduced scarring and C4d staining with donor pre-treatment for 7 days before transplantation. Grafts with conditional Ndst1 deficiency had reduced inflammation. Local inhibition of chemokine: GAG binding in donor organs immediately prior to transplant provides a new approach to reduce transplant damage and graft loss. Full article
(This article belongs to the Special Issue The Roles of Growth Factors, Cytokines and Their Receptors in Viral Infections)
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16 pages, 2650 KiB  
Article
Parapoxvirus Interleukin-10 Homologues Vary in Their Receptor Binding, Anti-Inflammatory, and Stimulatory Activities
by Amreen Naqash, Gabriella Stuart, Roslyn Kemp and Lyn Wise
Pathogens 2022, 11(5), 507; https://doi.org/10.3390/pathogens11050507 - 24 Apr 2022
Cited by 3 | Viewed by 2330
Abstract
Homologues of interleukin (IL)-10, a pleiotropic immunomodulatory cytokine, have been identified in the Parapoxvirus genus. The first identified, Orf virus (ORFV) IL-10, greatly enhanced infection of its host, exhibiting immune modulatory effects equivalent to human IL-10. IL-10-like genes were then identified in Bovine [...] Read more.
Homologues of interleukin (IL)-10, a pleiotropic immunomodulatory cytokine, have been identified in the Parapoxvirus genus. The first identified, Orf virus (ORFV) IL-10, greatly enhanced infection of its host, exhibiting immune modulatory effects equivalent to human IL-10. IL-10-like genes were then identified in Bovine papular stomatitis virus (BPSV), Pseudocowpox virus (PCPV), Red deerpox virus (RDPV) and Grey sealpox virus (GSPV). This study aimed to produce and characterise recombinant parapoxvirus IL-10s, then quantitatively compare their receptor binding and immunomodulatory activities. Recombinant IL-10s were expressed, purified, then characterised using bioinformatic, biochemical and enzymatic analyses. Anti-inflammatory effects were assessed in lipoteichoic acid-activated THP-1 monocytes, and stimulatory effects in MC/9 mast cells. IL-10 receptor (IL-10R)1 binding was detected in a competitive displacement assay. BPSV IL-10 inhibited production of monocyte chemoattractant protein (MCP)-1, IL-8 and IL-1β, induced mast cell proliferation, and bound IL-10R1 similarly to ORFV IL-10. PCPV IL-10 showed reduced MCP-1 inhibition, mast cell proliferation, and IL-10R1 binding. RDPV IL-10 displayed reduced inhibition of IL-8 and MCP-1 production. GSPV IL-10 showed limited inhibition of IL-1β production and stimulation of mast cell proliferation. These findings provide valuable insight into IL-10 receptor interactions, and suggest that the parapoxvirus IL-10s play similar pathogenic roles during infection of their hosts. Full article
(This article belongs to the Special Issue The Roles of Growth Factors, Cytokines and Their Receptors in Viral Infections)
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21 pages, 1164 KiB  
Systematic Review
The Role of Growth Factors in the Pathogenesis of Dengue: A Scoping Review
by Victor Edgar Fiestas Solórzano, Raquel Curtinhas de Lima and Elzinandes Leal de Azeredo
Pathogens 2022, 11(10), 1179; https://doi.org/10.3390/pathogens11101179 - 13 Oct 2022
Cited by 4 | Viewed by 3236
Abstract
Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping [...] Read more.
Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping review considered all published peer-reviewed studies in the MEDLINE and Embase databases. Ultimately, 58 studies that analyzed GFs in dengue patients, published between 1998 and 2021, were included. DENV-2 infection and secondary infection were more frequent in the patients studied. ELISA and multiplex immunoassay (Luminex) were the most used measurement techniques. Increased levels of vascular endothelial growth factor, granulocyte–macrophage colony-stimulating factor, granulocyte colony-stimulating factor, transforming growth factor beta, and hepatocyte growth factor as well as reduced levels of platelet-derived growth factor and epidermal growth factor were observed in severe dengue in most studies. Vascular endothelial growth factor and hepatocyte growth factor were identified as biomarkers of severity. In addition, there is evidence that the dengue virus can use the growth factor pathway to facilitate its entry into the cell and promote its viral replication. The use of tyrosine kinase inhibitors is an alternative treatment for dengue that is being studied. Full article
(This article belongs to the Special Issue The Roles of Growth Factors, Cytokines and Their Receptors in Viral Infections)
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