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Viral Receptors and Tropism

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

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 14449

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Special Issue Editor

Prof. Dr. Elmostafa Bahraoui

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Guest Editor

Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, France
Interests: RNA viruses; viral tropism; innate immune response; inflammatory responses; glycosylation; viral signaling; emerging viruses; vaccine development
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Special Issue Information

Dear Colleagues,

The first stage of the viral cycle is initiated by interactions between the virus and a series of molecules of different natures, including lipids, glycans and proteins. These host molecules can serve as an attachment receptor, receptor or coreceptor. During this first stage, signaling is activated to prepare for the entry of the virus and its transport to favorable compartments for its replication.

This Special Issue of Viruses is dedicated to viral receptors and tropism. We aim to present original works on various questions relating to, on the one hand, virus–host interaction, and on the other hand, the direct and indirect consequences of this interaction on the target cells and their functions. Thus, we encourage submissions focused on the following areas:

Characterization of virus–target cell interactions and determination of viral and cellular molecules, proteic or not, involved in this interaction;
Role of carbohydrates in host cell–virus tropism;
Evaluation of the signaling pathways activated following virus–target cell interaction and exploration of their effects on changes in the cell cytoskeleton and on the modification of cellular and viral proteins, including phosphorylation/dephosphorylation, acylation, ubiquitination, etc.;
Characterization of the mechanisms of penetration and intracellular trafficking of viruses in target cells;
Evaluation of the effects of cytokine/chemokines, including IFN-I, II, III, TNF-a, etc., in viral tropism;
Alternative unconventional viral entry pathways;
Relationships between viral induced pathogenicity and genetics, sex and aging.

Prof. Dr. Elmostafa Bahraoui
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

animal viruses
virus–cell host interactions
mechanisms of virus entry
viral signaling
intracellular trafficking
role of carbohydrates
viral uncoating
signaling pathways
relationships between genetics, sex and aging

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Published Papers (5 papers)

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Research

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20 pages, 6109 KiB

Open AccessArticle

The Biodistribution of Replication-Defective Simian Adenovirus 1 Vector in a Mouse Model

by Juan Chen, Xiaojuan Guo, Xiaohui Zou, Min Wang, Chunlei Yang, Wenzhe Hou, Matvey V. Sprindzuk and Zhuozhuang Lu

Viruses 2024, 16(4), 550; https://doi.org/10.3390/v16040550 - 31 Mar 2024

Viewed by 1497

Abstract

The administration route affects the biodistribution of a gene transfer vector and the expression of a transgene. A simian adenovirus 1 vector carrying firefly luciferase and GFP reporter genes (SAdV1-GFluc) were constructed, and its biodistribution was investigated in a mouse model by bioluminescence imaging and virus DNA tracking with real-time PCR. Luciferase activity and virus DNA were mainly found in the liver and spleen after the intravenous administration of SAdV1-GFluc. The results of flow cytometry illustrated that macrophages in the liver and spleen as well as hepatocytes were the target cells. Repeated inoculation was noneffective because of the stimulated serum neutralizing antibodies (NAbs) against SAdV-1. A transient, local expression of low-level luciferase was detected after intragastric administration, and the administration could be repeated without compromising the expression of the reporter gene. Intranasal administration led to a moderate, constant expression of a transgene in the whole respiratory tract and could be repeated one more time without a significant increase in the NAb titer. An immunohistochemistry assay showed that respiratory epithelial cells and macrophages in the lungs were transduced. High luciferase activity was restricted at the injection site and sustained for a week after intramuscular administration. A compromised transgene expression was observed after a repeated injection. When these mice were intramuscularly injected for a third time with the human adenovirus 5 (HAdV-5) vector carrying a luciferase gene, the luciferase activity recovered and reached the initial level, suggesting that the sequential use of SAdV-1 and HAdV-5 vectors was practicable. In short, the intranasal inoculation or intramuscular injection may be the preferred administration routes for the novel SAdV-1 vector in vaccine development. Full article

(This article belongs to the Special Issue Viral Receptors and Tropism)

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17 pages, 4142 KiB

Open AccessArticle

Unraveling DPP4 Receptor Interactions with SARS-CoV-2 Variants and MERS-CoV: Insights into Pulmonary Disorders via Immunoinformatics and Molecular Dynamics

by Arpan Narayan Roy, Aayatti Mallick Gupta, Deboshmita Banerjee, Jaydeb Chakrabarti and Pongali B. Raghavendra

Viruses 2023, 15(10), 2056; https://doi.org/10.3390/v15102056 - 6 Oct 2023

Cited by 7 | Viewed by 2469

Abstract

Human coronaviruses like MERS CoV are known to utilize dipeptidyl peptidase 4 (DPP4), apart from angiotensin-converting enzyme 2(ACE2) as a potential co-receptor for viral cell entry. DPP4, the ubiquitous membrane-bound aminopeptidase, is closely associated with elevation of disease severity in comorbidities. In SARS-CoV-2, there is inadequate evidence for combination of spike protein variants with DPP4, and underlying adversity in COVID-19. To elucidate this mechanistic basis, we have investigated interaction of spike protein variants with DPP4 through molecular docking and simulation studies. The possible binding interactions between the receptor binding domain (RBD) of different spike variants of SARS-CoV-2 and DPP4 have been compared with interactions observed in the experimentally determined structure of the complex of MERS-CoV with DPP4. Comparative binding affinity confers that Delta-CoV-2: DPP4 shows close proximity with MERS-CoV:DPP4, as depicted from accessible surface area, radius of gyration and number of hydrogen bonding in the interface. Mutations in the delta variant, L452R and T478K directly participate in DPP4 interaction, enhancing DPP4 binding. E484K in alpha and gamma variants of spike protein is also found to interact with DPP4. Hence, DPP4 interaction with spike protein becomes more suitable due to mutation, especially due to L452R, T478K and E484K. Furthermore, perturbation in the nearby residues Y495, Q474 and Y489 is evident due to L452R, T478K and E484K, respectively. Virulent strains of spike protein are more susceptible to DPP4 interaction and are prone to be victimized in patients due to comorbidities. Our results will aid the rational optimization of DPP4 as a potential therapeutic target to manage COVID-19 disease severity. Full article

(This article belongs to the Special Issue Viral Receptors and Tropism)

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Review

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17 pages, 1727 KiB

Open AccessReview

Cell Culture Adaptive Amino Acid Substitutions in FMDV Structural Proteins: A Key Mechanism for Altered Receptor Tropism

by Hassan Mushtaq, Syed Salman Shah, Yusra Zarlashat, Mazhar Iqbal and Wasim Abbas

Viruses 2024, 16(4), 512; https://doi.org/10.3390/v16040512 - 27 Mar 2024

Viewed by 1982

Abstract

The foot-and-mouth disease virus is a highly contagious and economically devastating virus of cloven-hooved animals, including cattle, buffalo, sheep, and goats, causing reduced animal productivity and posing international trade restrictions. For decades, chemically inactivated vaccines have been serving as the most effective strategy for the management of foot-and-mouth disease. Inactivated vaccines are commercially produced in cell culture systems, which require successful propagation and adaptation of field isolates, demanding a high cost and laborious time. Cell culture adaptation is chiefly indebted to amino acid substitutions in surface-exposed capsid proteins, altering the necessity of RGD-dependent receptors to heparan sulfate macromolecules for virus binding. Several amino acid substations in VP1, VP2, and VP3 capsid proteins of FMDV, both at structural and functional levels, have been characterized previously. This literature review combines frequently reported amino acid substitutions in virus capsid proteins, their critical roles in virus adaptation, and functional characterization of the substitutions. Furthermore, this data can facilitate molecular virologists to develop new vaccine strains against the foot-and-mouth disease virus, revolutionizing vaccinology via reverse genetic engineering and synthetic biology. Full article

(This article belongs to the Special Issue Viral Receptors and Tropism)

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48 pages, 4902 KiB

Open AccessReview

Natural Adeno-Associated Virus Serotypes and Engineered Adeno-Associated Virus Capsid Variants: Tropism Differences and Mechanistic Insights

by Estrella Lopez-Gordo, Kyle Chamberlain, Jalish Mahmud Riyad, Erik Kohlbrenner and Thomas Weber

Viruses 2024, 16(3), 442; https://doi.org/10.3390/v16030442 - 12 Mar 2024

Cited by 5 | Viewed by 7223 | Correction

Abstract

Today, adeno-associated virus (AAV)-based vectors are arguably the most promising in vivo gene delivery vehicles for durable therapeutic gene expression. Advances in molecular engineering, high-throughput screening platforms, and computational techniques have resulted in a toolbox of capsid variants with enhanced performance over parental serotypes. Despite their considerable promise and emerging clinical success, there are still obstacles hindering their broader use, including limited transduction capabilities, tissue/cell type-specific tropism and penetration into tissues through anatomical barriers, off-target tissue biodistribution, intracellular degradation, immune recognition, and a lack of translatability from preclinical models to clinical settings. Here, we first describe the transduction mechanisms of natural AAV serotypes and explore the current understanding of the systemic and cellular hurdles to efficient transduction. We then outline progress in developing designer AAV capsid variants, highlighting the seminal discoveries of variants which can transduce the central nervous system upon systemic administration, and, to a lesser extent, discuss the targeting of the peripheral nervous system, eye, ear, lung, liver, heart, and skeletal muscle, emphasizing their tissue and cell specificity and translational promise. In particular, we dive deeper into the molecular mechanisms behind their enhanced properties, with a focus on their engagement with host cell receptors previously inaccessible to natural AAV serotypes. Finally, we summarize the main findings of our review and discuss future directions. Full article

(This article belongs to the Special Issue Viral Receptors and Tropism)

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