Modeling Human Respiratory Viral Infections in the Cotton Rat (Sigmodon hispidus)

Blanco, Jorge C. G.; Boukhvalova, Marina S.; Pérez, Daniel R.; Vogel, Stefanie N.; Kajon, Adriana E.

doi:10.4172/jaa.1000093

Cited by 20 publications

(14 citation statements)

References 22 publications

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“…In addition, the course of influenza virus infection and associated histopathological changes seen in cotton rats are more relevant to human infection and disease than in the mouse model ( 27 ). Importantly, cotton rats are permissive to infections with most of the common human viral respiratory pathogens, including RSV, HRVs, human metapneumovirus, human parainfluenza virus, adenoviruses, enterovirus D68, and measles virus, making this species an excellent model for studying human respiratory viruses ( 30 – 32 , 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

Patel

Shirey

Boukhvalova

et al. 2018

mBio

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Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI.

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Section: Discussionmentioning

confidence: 99%

Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

Patel

Shirey

Boukhvalova

et al. 2018

mBio

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“…mice. In contrast to mice which usually require the use of mouse adapted influenza virus strains for challenge (Bouvier & Lowen, 2010 ), cotton rats are susceptible to infection by unadapted, human influenza virus strains (Eichelberger et al., 2004 ; Ottolini et al., 2005 ; Blanco et al., 2014 ). Disease progression in cotton rats is symptomatic and can be frequently monitored by measuring breathing frequency, weight loss, and temperature drop (Eichelberger et al., 2004 ; Ottolini et al., 2005 ; Blanco et al., 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus

et al. 2018

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Administration of influenza vaccines to the lungs could be an attractive alternative to conventional parenteral administration. In this study, we investigated the deposition site of pulmonary delivered liquid and powder influenza vaccine formulations and its relation to their immunogenicity and protective efficacy. In vivo deposition studies in cotton rats revealed that, the powder formulation was mainly deposited in the trachea ( ∼ 65%) whereas the liquid was homogenously distributed throughout the lungs ( ∼ 96%). In addition, only 60% of the antigen in the powder formulation was deposited in the respiratory tract with respect to the liquid formulation. Immunogenicity studies showed that pulmonary delivered liquid and powder influenza formulations induced robust systemic and mucosal immune responses (significantly higher by liquids than by powders). When challenged with a clinical isolate of homologous H1N1pdm virus, all animals pulmonary administered with placebo had detectable virus in their lungs one day post challenge. In contrast, none of the vaccinated animals had detectable lung virus titers, except for two out of eight animals from the powder immunized group. Also, pulmonary vaccinated animals showed no or little signs of infection like increase in breathing frequency or weight loss upon challenge as compared to animals from the negative control group. In conclusion, immune responses induced by liquid formulation were significantly higher than responses induced by powder formulation, but the overall protective efficacy of both formulations was comparable. Thus, pulmonary immunization is capable of inducing protective immunity and the site of antigen deposition seems to be of minor relevance in inducing protection.

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“…Guinea pigs have been used as a model of transmission of influenza viruses (16); however, even though the H5N1 and 1918 pandemic viruses replicated in the lungs and nasal turbinates of these animals, no weight loss or morbidity was observed (17). Recently, cotton rats have been considered a potential animal model for influenza viruses (18). They are susceptible to both human influenza A and B viruses without prior adaptation (19)(20)(21)(22), and an H5N1 virus was shown to be lethal in this species (22).…”

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confidence: 99%

Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection

Iwatsuki‐Horimoto

Nakajima

Ichiko

et al. 2018

J Virol

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Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses.

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Modeling Human Respiratory Viral Infections in the Cotton Rat (Sigmodon hispidus)

Cited by 20 publications

References 22 publications

Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus

Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection

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