scholarly journals Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 92 ◽  
Author(s):  
Venkatraman Siddharthan ◽  
Jinxin Miao ◽  
Arnaud Van Wettere ◽  
Rong Li ◽  
Hua Wu ◽  
...  
Keyword(s):  
Zika Virus ◽  
Polyclonal Antibodies ◽  
Small Animal ◽  
Significant Protection ◽  
Small Animal Model ◽  
Zikv Infection ◽  
Hamster Model ◽  
Congenital Diseases ◽  
Syrian Hamsters ◽  
Testicular Lesions

Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain–Barré syndrome in adults. Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection. Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically. These antibodies also prevent testicular lesions in this hamster model. Our data indicate that antibody-mediated immunotherapy is effective in treating ZIKV infection. Because suitable quantities of highly potent human polyclonal antibodies can be quickly produced from the TcB system against ZIKV and have demonstrated therapeutic efficacy in a small animal model, they have the potential as an effective countermeasure against ZIKV infection.

scholarly journals Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development

2020 ◽  
pp. 202009799 ◽  
Author(s):  
Masaki Imai ◽  
Kiyoko Iwatsuki-Horimoto ◽  
Masato Hatta ◽  
Samantha Loeber ◽  
Peter J. Halfmann ◽  
...  
Keyword(s):  
Global Economy ◽  
Human Lung ◽  
Small Animal ◽  
Ground Glass Opacity ◽  
Neutralizing Antibody ◽  
Hamster Model ◽  
Syrian Hamsters ◽  
Lung Consolidation ◽  
Novel Coronavirus ◽  
Severe Lung

At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy. Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters. SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection. In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2−infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation. SARS-CoV-2−infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters. Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs.

scholarly journals Route of Infection Influences Zika Virus Shedding in a Guinea Pig Model

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1437 ◽  
Author(s):  
Ashley E. Saver ◽  
Stephanie A. Crawford ◽  
Jonathan D. Joyce ◽  
Andrea S. Bertke
Keyword(s):  
Animal Models ◽  
Guinea Pig ◽  
Zika Virus ◽  
Sexual Transmission ◽  
Clinical Signs ◽  
Small Animal ◽  
Small Sample ◽  
Zikv Infection ◽  
Virus Shedding ◽  
Route Of Infection

Due to the recent epidemic of Zika virus (ZIKV) infection and resulting sequelae, as well as concerns about both the sexual and vertical transmission of the virus, renewed attention has been paid to the pathogenesis of this unique arbovirus. Numerous small animal models have been used in various ZIKV pathogenicity studies, however, they are often performed using immunodeficient or immunosuppressed animals, which may impact disease progression in a manner not relevant to immunocompetent humans. The use of immunocompetent animal models, such as macaques, is constrained by small sample sizes and the need for specialized equipment/staff. Here we report the establishment of ZIKV infection in an immunocompetent small animal model, the guinea pig, using both subcutaneous and vaginal routes of infection to mimic mosquito-borne and sexual transmission. Guinea pigs developed clinical signs consistent with mostly asymptomatic and mild disease observed in humans. We demonstrate that the route of infection does not significantly alter viral tissue tropism but does impact mucosal shedding mechanics. We also demonstrate persistent infection in sensory and autonomic ganglia, identifying a previously unrecognized niche of viral persistence that could contribute to viral shedding in secretions. We conclude that the guinea pig represents a useful and relevant model for ZIKV pathogenesis.

scholarly journals Three Immunocompetent Small Animal Models That Do Not Support Zika Virus Infection

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 971
Author(s):  
Megan R. Miller ◽  
Anna C. Fagre ◽  
Taylor C. Clarkson ◽  
Erin D. Markle ◽  
Brian D. Foy
Keyword(s):  
Animal Model ◽  
New Zealand ◽  
Animal Models ◽  
Zika Virus ◽  
Guinea Pigs ◽  
Sexual Transmission ◽  
Small Animal ◽  
Zikv Infection ◽  
Mosquito Bite ◽  
Multimammate Mice

Zika virus (ZIKV) is a mosquito-borne flavivirus that is primarily transmitted to humans through the bite of an infected mosquito. ZIKV causes disease in infected humans with added complications of Guillain-Barré syndrome and birth defects in infants born to mothers infected during pregnancy. There are several large immunocompetent animal models for ZIKV including non-human primates (NHPs). NHP models closely reflect human infection; however, due to sample size restrictions, investigations into the effects of transmission route and the impacts on disease dynamics have been understudied. Mice have been widely used for modeling ZIKV infection, yet there are few ZIKV-susceptible immunocompetent mouse models and none of these have been used to investigate sexual transmission. In an effort to identify a small immunocompetent animal model to characterize sexual transmission of ZIKV, we attempt experimental infection of multimammate mice, New Zealand white rabbits, and Hartley guinea pigs. The multimammate mouse is the natural reservoir of Lassa fever virus and has been identified to harbor other human pathogens. Likewise, while NZW rabbits are susceptible to West Nile virus, they have not yet been examined for their susceptibility to infection with ZIKV. Guinea pigs have been successfully used as models for ZIKV infection, but only in immunocompromised life stages (young or pregnant). Here, it was found that the multimammate mouse and New Zealand White (NZW) rabbits are not susceptible ZIKV infection as determined by a lack viral RNA in tissues and fluids collected. Sexually mature male Hartley guinea pigs were inoculated subcutaneously and by mosquito bite, but found to be refractory to ZIKV infection, contrary to findings of other studies in young and pregnant guinea pigs. Interestingly, here it is shown that adult male guinea pigs are not susceptible to ZIKV infection, even when infected by natural route (e.g., mosquito bite). Although a new small animal model for the sexual transmission for ZIKV was not established through this study, these findings provide information on outbred animal species that are not permissive to infection (NZW rabbits and multimammate mice) and new information surrounding limitations of a previously established animal model (guinea pigs).

scholarly journals Syrian hamster as an animal model for the study of human influenza virus infection

2017 ◽  
pp. JVI.01693-17 ◽  
Author(s):  
Kiyoko Iwatsuki-Horimoto ◽  
Noriko Nakajima ◽  
Yurie Ichiko ◽  
Yuko Sakai-Tagawa ◽  
Takeshi Noda ◽  
...  
Keyword(s):  
Animal Model ◽  
Virus Infection ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Small Animal ◽  
Influenza Viruses ◽  
Human Influenza ◽  
Small Animal Model ◽  
Syrian Hamsters ◽  
B Virus

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 them as an alternative animal model to mice. 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 pdm09 and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were airborne transmissible in these hamsters. Hamsters thus have potential as 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 H1N1 virus transmission studies.IMPORTANCEWe found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested are airborne transmitted in these hamsters. Syrian hamsters thus have potential as a small animal model for the study of human influenza viruses.

scholarly journals Zika virus infection in Collaborative Cross mice

2019 ◽  
Author(s):  
Melissa D. Mattocks ◽  
Kenneth S. Plante ◽  
Ethan J. Fritch ◽  
Ralph S. Baric ◽  
Martin T. Ferris ◽  
...  
Keyword(s):  
Weight Loss ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Laboratory Mouse ◽  
Small Animal ◽  
Collaborative Cross ◽  
Zikv Infection ◽  
Pathogenic Mechanisms ◽  
Low Levels

AbstractThe 2015-2016 emergence of Zika virus (ZIKV) in the Americas, and recognition that ZIKV infection during pregnancy can result in birth defects, revealed a need for small animal models to study ZIKV pathogenic mechanisms and evaluate candidate vaccines and antivirals. Mice would be an attractive system for such studies, but ZIKV replicates poorly in laboratory mice because it fails to antagonize murine STAT2 and STING. To address this, most ZIKV pathogenesis studies have used mice with impaired interferon signaling (e.g. Ifnar1−/− or treatment with IFNAR1-blocking antibodies). However, using mice with severe defects in innate antiviral signaling confounds studies of viral pathogenic mechanisms. Collaborative Cross (CC) mice have proven to be a valuable system for developing new mouse pathogenesis models for viral infections that are not well modeled in conventional laboratory mouse lines. To test whether CC mice could provide an immune-competent model for ZIKV pathogenesis, we infected CC lines with ZIKV and assessed weight loss, viremia, and production of neutralizing antibodies. We tested 21 CC lines (CC001, CC002, CC003, CC004, CC005, CC006, CC011, CC012, CC013, CC019, CC024, CC028, CC040, CC041, CC042, CC046, CC051, CC059, CC061, CC068, and CC072, 13 of which have non-functional alleles of the flavivirus restriction factor Oas1b) and 3 ZIKV strains (MR766, H/PF/2013, and a mouse-adapted variant of Dakar 41525). ZIKV infection did not induce weight loss compared to mock-infected controls and accordingly only low levels of viral RNA were detected in serum. Only a subset of mice developed neutralizing antibodies to ZIKV, likely due to overall low levels of infection and viremia. Our results are consistent with other studies demonstrating poor ZIKV infection in interferon-intact mice and suggest that the tested CC lines do not include polymorphic host genes that greatly increase susceptibility to ZIKV infection.

scholarly journals Pathogenesis and transmission of SARS-CoV-2 virus in golden Syrian hamsters

2020 ◽  
Author(s):  
Sin Fun Sia ◽  
Li-Meng Yan ◽  
Alex WH Chin ◽  
Kevin Fung ◽  
Leo LM Poon ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Neutralizing Antibodies ◽  
Global Economy ◽  
Small Animal ◽  
The Body ◽  
Post Inoculation ◽  
The Novel ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Syrian Hamsters

Abstract A pandemic caused by the novel SARS-CoV-2 virus with high nucleotide identity to SARS-CoV and SARS-related coronaviruses detected in horseshoe bats is spreading across the world and impacting the healthcare systems and global economy1,2. A suitable small animal model is urgently needed to support the development of vaccines and antiviral treatments against the SARS-CoV-2 virus. We report the pathogenesis and transmissibility of the SARS-CoV-2 in the golden Syrian hamster model. The SARS-CoV-2 virus replicated in the epithelial cells of respiratory and gastrointestinal tracts. Immunohistochemistry demonstrated viral antigens in the areas of lung consolidation on day 2 and 5 post- inoculation, followed by rapid viral clearance and tissue repairing on day 7. Viral antigen was also detected in the epithelial cells of duodenum without apparent inflammatory response on day 2. Notably, we observed that the SARS-CoV-2 virus can be transmitted efficiently from the inoculated hamsters to co-housed naïve contact hamsters. The inoculated hamsters and naturally-infected hamsters lost greater than 10% of the body weight, and all animals recovered with the detection of neutralizing antibodies within 14 days. Our results suggest that SARS-CoV-2 infection in golden Syrian hamsters resemble features found in human patients with mild infections.Authors Sin Fun Sia, Li-Meng Yan, and Alex WH Chin contributed equally to this work.

scholarly journals Recapitulating Zika Virus Infection in Vagina of Tree Shrew (Tupaia belangeri)

2021 ◽  
Vol 11 ◽  
Author(s):  
Zulqarnain Baloch ◽  
Zhili Shen ◽  
Li Zhang ◽  
Yue Feng ◽  
Daoqun Li ◽  
...  
Keyword(s):  
Animal Model ◽  
Viral Load ◽  
Zika Virus ◽  
Tree Shrew ◽  
Sexual Transmission ◽  
Small Animal ◽  
Female Reproductive Tract ◽  
Small Animal Model ◽  
Tree Shrews ◽  
Female Tree

Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01 via the intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetus in vivo.

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