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Viruses
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Animal Models for Virology Research
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Animal Models for Virology Research

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

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 11682

Special Issue Editors

Dr. Bart Tarbet

E-Mail Website
Guest Editor
Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, UT 84322, USA
Interests: enterovirus; influenza virus; animal model
Dr. Brett L. Hurst

E-Mail Website
Guest Editor
Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, UT 84322, USA
Interests: immune response; animal model

Special Issue Information

Dear Colleagues,

The use of cell culture models in virology is critical to understand the cell and molecular biology of virus infections. However, cell culture models have limitations, in that they do not allow the evaluation of virus tissue tropism, virus spread and pathogenesis in the host, or the host immune response to infection. Animal models are required to establish the natural history (time course) of infection from initial virus exposure, spread within the host, pathogenesis and clinical signs, and the host response to infection, until the outcome of recovery from illness or mortality.

This Special Issue aims to provide an overview of animal models used for virology research. Models used for the study of viral pathogenesis and the immune response to infection, including models used to evaluate the efficacy of antiviral therapeutics and vaccines, will be emphasized. The goal of this Special Issue is to stimulate future research and innovation in this important and challenging field.

Dr. Bart Tarbet
Dr. Brett L. Hurst
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

  • animal model
  • viral pathogenesis
  • antiviral therapeutics
  • therapeutic models
  • vaccine models

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Published Papers (7 papers)

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Research

Jump to: Review

20 pages, 5922 KiB  
Article
Differences in Susceptibility to SARS-CoV-2 Infection Among Transgenic hACE2-Hamster Founder Lines
by Scott A. Gibson, Yanan Liu, Rong Li, Brett L. Hurst, Zhiqiang Fan, Venkatraman Siddharthan, Deanna P. Larson, Ashley Y. Sheesley, Rebekah Stewart, Madelyn Kunzler, Irina A. Polejaeva, Arnaud J Van Wettere, Stefan Moisyadi, John D. Morrey, E. Bart Tarbet and Zhongde Wang
Viruses 2024, 16(10), 1625; https://doi.org/10.3390/v16101625 - 17 Oct 2024
Viewed by 816
Abstract
Animal models that are susceptible to SARS-CoV-2 infection and develop clinical signs like human COVID-19 are desired to understand viral pathogenesis and develop effective medical countermeasures. The golden Syrian hamster is important for the study of SARS-CoV-2 since hamsters are naturally susceptible to [...] Read more.
Animal models that are susceptible to SARS-CoV-2 infection and develop clinical signs like human COVID-19 are desired to understand viral pathogenesis and develop effective medical countermeasures. The golden Syrian hamster is important for the study of SARS-CoV-2 since hamsters are naturally susceptible to SARS-CoV-2. However, infected hamsters show only limited clinical disease and resolve infection quickly. In this study, we describe development of human angiotensin-converting enzyme 2 (hACE2) transgenic hamsters as a model for COVID-19. During development of the model for SARS-CoV-2, we observed that different hACE2 transgenic hamster founder lines varied in their susceptibility to SARS-CoV-2 lethal infection. The highly susceptible hACE2 founder lines F0F35 and F0M41 rapidly progress to severe infection and death within 6 days post-infection (p.i.). Clinical signs included lethargy, weight loss, dyspnea, and mortality. Lethality was observed in a viral dose-dependent manner with a lethal dose as low as 1 × 100.15 CCID50. In addition, virus shedding from highly susceptible lines was detected in oropharyngeal swabs on days 2–5 p.i., and virus titers were observed at 105.5−6.5 CCID50 in lung and brain tissue by day 4 p.i.. Histopathology revealed that infected hACE2-hamsters developed rhinitis, tracheitis, bronchointerstitial pneumonia, and encephalitis. Mortality in highly susceptible hACE2-hamsters can be attributed to neurologic disease with contributions from the accompanying respiratory disease. In contrast, virus challenge of animals from less susceptible founder lines, F0M44 and F0M51, resulted in only 0–20% mortality. To demonstrate utility of this SARS-CoV-2 infection model, we determined the protective effect of the TLR3 agonist polyinosinic-polycytidylic acid (Poly (I:C)). Prophylactic treatment with Poly (I:C) significantly improved survival in highly susceptible hACE2-hamsters. In summary, our studies demonstrate that hACE2 transgenic hamsters differ in their susceptibility to SARS-CoV-2 infection, based on the transgenic hamster founder line, and that prophylactic treatment with Poly (I:C) was protective in this COVID-19 model of highly susceptible hACE2-hamsters. Full article
(This article belongs to the Special Issue Animal Models for Virology Research)
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13 pages, 2787 KiB  
Article
Adapting Real-Time Lung Function Measurements for SARS-CoV-2 Infection Studies in Syrian Hamsters
by Rineke de Jong, Wout Nuiten, Albertjan ter Heide, Wilfred Hamstra, Sandra Vreman, Nadia Oreshkova, Katrin E. Wiese and Nora M. Gerhards
Viruses 2024, 16(7), 1022; https://doi.org/10.3390/v16071022 - 25 Jun 2024
Viewed by 1109
Abstract
Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge [...] Read more.
Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge the gap between preclinical and clinical readouts, we aimed to apply unrestrained whole-body plethysmography (WBP) measurements in a SARS-CoV-2 Syrian hamster challenge model. While WBP measurements are frequently used for preclinical research in mice and rats, results from studies in hamsters are still limited. During unrestrained WBP measurements, we obtained highly variable breathing frequency values outside of the normal physiological range for hamsters. Importantly, we observed that animal movements were recorded as breaths during WBP measurements. By limiting animal movement through either mechanical or chemical restraint, we improved the reliability of the lung function readout and obtained breathing frequencies that correlated with clinical signs when comparing two different variants of SARS-CoV-2 post-inoculation. Simultaneously, however, new sources of experimental variation were introduced by the method of restraint, which demands further optimalization of WBP measurements in Syrian hamsters. We concluded that WBP measurements are a valuable refinement either in combination with video recordings or if average values of measurements lasting several hours are analyzed. Full article
(This article belongs to the Special Issue Animal Models for Virology Research)
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22 pages, 3750 KiB  
Article
Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters
by Caterina Di Pietro, Ann M. Haberman, Brett D. Lindenbach, Peter C. Smith, Emanuela M. Bruscia, Heather G. Allore, Brent Vander Wyk, Antariksh Tyagi and Caroline J. Zeiss
Viruses 2024, 16(2), 246; https://doi.org/10.3390/v16020246 - 3 Feb 2024
Cited by 2 | Viewed by 2131
Abstract
Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza [...] Read more.
Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates. Full article
(This article belongs to the Special Issue Animal Models for Virology Research)
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14 pages, 1903 KiB  
Article
Exploring the Susceptibility of C3H Mice to Tick-Borne Encephalitis Virus Infection: Implications for Co-Infection Models and Understanding of the Disease
by Stefania Porcelli, Aurélie Heckmann, Anne-Claire Lagrée, Clémence Galon, Sara Moutailler and Pierre Lucien Deshuillers
Viruses 2023, 15(11), 2270; https://doi.org/10.3390/v15112270 - 17 Nov 2023
Cited by 3 | Viewed by 1642
Abstract
Ticks and tick-borne diseases (TBDs) are increasingly recognized as a critical One Health concern. Tick-borne encephalitis (TBE), a severe neuro infection caused by the tick-borne encephalitis virus (TBEV), has emerged as a significant global public health threat. Laboratory animals, particularly mice, have played [...] Read more.
Ticks and tick-borne diseases (TBDs) are increasingly recognized as a critical One Health concern. Tick-borne encephalitis (TBE), a severe neuro infection caused by the tick-borne encephalitis virus (TBEV), has emerged as a significant global public health threat. Laboratory animals, particularly mice, have played a pivotal role in advancing our understanding of TBD pathogenesis. Notably, BALB/c mice have been employed as models due to their heightened susceptibility to TBEV. However, the use of C3H mice, valued for other tick-borne pathogens, has remained unexplored for TBEV until now. This study aimed to assess the susceptibility of C3H mice to TBEV infection, laying the groundwork for future co-infection models involving TBEV and Borrelia. Experiments revealed that C3H mice are susceptible to TBEV infection through subcutaneous inoculation. While 102 PFU/mouse appeared necessary for full infection, 103 PFU/mouse induced consistent symptoms. However, subsequent assessment of ticks’ acquisition of TBEV from infected mice met with limited success, raising questions about optimal infectious doses for natural infection. These findings suggest the potential of C3H mice for studying TBEV and co-infections with other pathogens, particularly Borrelia. Further exploration of the interplay between these pathogens, their transmission dynamics, and disease severity could enhance prevention and control strategies. Full article
(This article belongs to the Special Issue Animal Models for Virology Research)
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Review

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17 pages, 951 KiB  
Review
Rapid Development of Small Rodent Animal Models for Infectious Disease Research Through Vectorized Receptor Molecule Expression
by Melanie M. Goens, Erin L. Howard, Bryce M. Warner, Leonardo Susta and Sarah K. Wootton
Viruses 2024, 16(11), 1794; https://doi.org/10.3390/v16111794 - 19 Nov 2024
Viewed by 524
Abstract
The emergence and re-emergence of pathogens with pandemic potential has been a persistent issue throughout history. Recent decades have seen significant outbreaks of zoonotic viruses from members of the Coronaviridae, Filoviridae, Paramyxoviridae, Flaviviridae, and Togaviridae families, resulting in widespread [...] Read more.
The emergence and re-emergence of pathogens with pandemic potential has been a persistent issue throughout history. Recent decades have seen significant outbreaks of zoonotic viruses from members of the Coronaviridae, Filoviridae, Paramyxoviridae, Flaviviridae, and Togaviridae families, resulting in widespread infections. The continual emergence of zoonotic viral pathogens and associated infections highlights the need for prevention strategies and effective treatments. Central to this effort is the availability of suitable animal models, which are essential for understanding pathogenesis and assessing transmission dynamics. These animals are also critical for evaluating the safety and efficacy of novel vaccines or therapeutics and are essential in facilitating regulatory approval of new products. Rapid development of animal models is an integral aspect of pandemic response and preparedness; however, their establishment is fraught by several rate-limiting steps, including selection of a suitable species, the logistical challenges associated with sharing and disseminating transgenic animals (e.g., the time-intensive nature of breeding and maintaining colonies), the availability of technical expertise, as well as ethical and regulatory approvals. A method for the rapid development of relevant animal models that has recently gained traction, in large part due to the COVID-19 pandemic, is the use of gene therapy vectors to express human viral receptors in readily accessible laboratory animals to enable virus infection and development of clinical disease. These models can be developed rapidly on any genetic background, making mechanistic studies and accelerated evaluation of novel countermeasures possible. In this review, we will discuss important considerations for the effective development of animal models using viral vector approaches and review the current vector-based animal models for studying viral pathogenesis and evaluating prophylactic and therapeutic strategies, with an emphasis on models of SARS-CoV-2 infection based on the vectorized expression of human angiotensin-converting enzyme 2. Full article
(This article belongs to the Special Issue Animal Models for Virology Research)
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15 pages, 823 KiB  
Review
Small Animal Models to Study Herpes Simplex Virus Infections
by Mohammed Tanveer Hussain, Brent A. Stanfield and David I. Bernstein
Viruses 2024, 16(7), 1037; https://doi.org/10.3390/v16071037 - 27 Jun 2024
Viewed by 2065
Abstract
Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The [...] Read more.
Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The seropositive rate for HSV-1 is around 90%, whereas for HSV-2 it remains around 20–25% for the general adult population. The infections caused by these viruses remain difficult to study because a large proportion of infected individuals are asymptomatic. Furthermore, given the neurotropic characteristics of the virus, studies aimed at understanding the complex pathogenesis in humans is difficult. As a result, animal models have been developed to understand several characteristics of HSV biology, pathogenesis, disease and host responses to infection. These models are also commonly used as the first evaluation of new drugs and vaccines. There are several well-established animal models to study infection with HSV, including mice, guinea pigs and rabbits. Variables within the animal models depend on the species of animal, route of infection, viral strain, dosage, etc. This review aims at summarizing the most commonly used animal models to study HSV pathogenesis and therapies. Full article
(This article belongs to the Special Issue Animal Models for Virology Research)
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39 pages, 673 KiB  
Review
Experimental Infection Models and Their Usefulness for White Spot Syndrome Virus (WSSV) Research in Shrimp
by Natasja Cox, Evelien De Swaef, Mathias Corteel, Wim Van Den Broeck, Peter Bossier, Hans J. Nauwynck and João J. Dantas-Lima
Viruses 2024, 16(5), 813; https://doi.org/10.3390/v16050813 - 20 May 2024
Cited by 1 | Viewed by 2372
Abstract
White spot syndrome virus (WSSV) is marked as one of the most economically devastating pathogens in shrimp aquaculture worldwide. Infection of cultured shrimp can lead to mass mortality (up to 100%). Although progress has been made, our understanding of WSSV’s infection process and [...] Read more.
White spot syndrome virus (WSSV) is marked as one of the most economically devastating pathogens in shrimp aquaculture worldwide. Infection of cultured shrimp can lead to mass mortality (up to 100%). Although progress has been made, our understanding of WSSV’s infection process and the virus–host–environment interaction is far from complete. This in turn hinders the development of effective mitigation strategies against WSSV. Infection models occupy a crucial first step in the research flow that tries to elucidate the infectious disease process to develop new antiviral treatments. Moreover, since the establishment of continuous shrimp cell lines is a work in progress, the development and use of standardized in vivo infection models that reflect the host–pathogen interaction in shrimp is a necessity. This review critically examines key aspects of in vivo WSSV infection model development that are often overlooked, such as standardization, (post)larval quality, inoculum type and choice of inoculation procedure, housing conditions, and shrimp welfare considerations. Furthermore, the usefulness of experimental infection models for different lines of WSSV research will be discussed with the aim to aid researchers when choosing a suitable model for their research needs. Full article
(This article belongs to the Special Issue Animal Models for Virology Research)
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