Zika Virus Infection in Syrian Golden Hamsters and Strain 13 Guinea Pigs

Miller, Lynn J.; Nasar, Farooq; Schellhase, Christopher W.; Norris, Sarah L.; Kimmel, Adrienne; Valdez, Stephanie M.; Wollen-Roberts, Suzanne E.; Shamblin, Joshua D.; Sprague, Thomas R.; Lugo‐Roman, Luis A.; Jarman, Richard G.; Yoon, In-Kyu; Alera, Maria Theresa; Bavari, Sina; Pitt, M. Louise M.; Haddow, Andrew D.

doi:10.4269/ajtmh.17-0686

Cited by 20 publications

(11 citation statements)

References 29 publications

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“…A low-level viremia was detected via RT-qPCR in the serum of both groups throughout the study. Most current models were unable to detect viremia beyond 5 dpi; however, one model reported detection of low-level viremia up to 14 dpi, and one reported no detection at any time point [56,57,58,59]. Our detection of a sustained and persistent low-level serum viremia in both SQ and VAG infected groups up to 37 dpi represents the longest detection of serum viremia in a guinea pig model.…”

Section: Discussionmentioning

confidence: 68%

“…Similarly, SQ inoculation of male guinea pigs with strain GZ01 (Venezuela) or FSS13025 (Cambodia) resulted in viremia and robust viral secretion in saliva and tears, as well as transmission to naïve co-caged mates, but no overt signs of disease [57]. However, intracerebral infection with strain MR766 (Uganda) or intraperitoneal inoculation with strain ArD41525 (Senegal) or CPC-0740 (Philippines) failed to produce signs of infection or viremia [1,58]. An additional study assessed fetal impact of mid-gestation infection in guinea pigs, finding viremia and robust antibody response following SQ inoculation with strain H/PF/2013 (French Polynesia) without effects on pups [59].…”

Section: Introductionmentioning

confidence: 99%

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

Saver

Crawford

Joyce

et al. 2019

Cells

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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.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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

Saver

Crawford

Joyce

et al. 2019

Cells

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“…Thus, the use of diverse model systems is necessary for providing a better understanding of the molecular mechanisms underlying behavior and disease. For examples, hamsters are a preferred model for investigating reproductive biology 14 , tumor growth 22,23 , and more recently in studying properties of infectious diseases, including Ebola, Zika, and influenza viruses 17,18,24,25 . Furthermore, the human stress response system is more similar to the hamster system than to that of other rodent models and both male and female hamsters readily exhibit aggressive behavior, making hamsters an excellent model to investigate behavioral, physiological, and molecular responses to social stress in both sexes 10,11,16 .…”

Section: Discussionmentioning

confidence: 99%

Binding affinities of oxytocin, vasopressin and Manning compound at oxytocin and V1a receptors in male Syrian hamster brains

Taylor

McCann

Ross

et al. 2020

J Neuroendocrinology

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Oxytocin (OT) and arginine vasopressin (AVP), as well as synthetic ligands targeting their receptors (OTR, V1aR), are used in a wide variety of research contexts, but typically their pharmacological properties are determined in only a few species. Syrian hamsters (Mesocricetus auratus) have a long history of use as a behavioral and biomedical model for the study of oxytocin and vasopressin, and more recently, hamsters have been used to investigate behavioral consequences of OT-mediated activation of V1aRs. We sought to determine the binding affinities of OT, AVP, and the selective V1aR antagonist, Manning compound, in OTRs and V1aRs found in hamster brains. We performed saturation binding asays to determine the Kd values for the selective OTR and V1aR radioligands, [125I]OVTA and [125I]LVA in hamster brains. We then performed competition binding assays to determine Ki values for OT, AVP, and Manning compond at both the OTR and V1aR. We found that OT and AVP each had the highest affinity for their canonical receptors (OT-OTR Ki=4.28 nM; AVP-V1ar Ki=4.70 nM), and had the lowest affinity for their non-canonical ligands (OT-V1aR=495.2nM; AVP-OTR Ki=36.1 nM). Manning compound had the highest affinity for the V1aR (MC-V1aR Ki=6.87 nM; MC-OTR Ki=213.8 nM), but Manning compound was not as selective for the V1aR as has been reported in rat receptor. When comparing these data to previously published work, we found that the promiscuity of the V1aR in hamsters with respect to oxytocin and vasopressin binding is more similar to the promiscuity of the human V1aR than the rat V1aR receptor. Moreover, the selectivity of oxytocin at hamster receptors is more similar to the selectivity of oxytocin at human receptors than the selectivity of oxytocin at rat receptors. These data highlight the importance of determining the pharmacological properties of behaviorally relevant compounds in diverse models species.

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“…Robert Tesh and Scott Weaver at the University of Texas Medical Branch. We selected this strain due to its low passage history, an intact N-linked glycosylation site [ 12 , 86 , 87 ], the results of in vivo and in vitro characterization studies [ 87 , 88 ], and its ability to initiate systemic infection in rhesus and cynomolgus macaques following intravaginal or intrarectal inoculation [ 79 ]. Furthermore, this strain was isolated in a region within the known distribution of AGMs.…”

Section: Methodsmentioning

confidence: 99%

Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey

et al. 2020

Self Cite

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Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we modeled mosquito and sexual transmission of ZIKV in the African green monkey (AGM). Following subcutaneous, intravaginal or intrarectal inoculation of AGMs with ZIKV, we determined the transmission potential and infection dynamics of the virus. AGMs inoculated by all three transmission routes exhibited viremia and viral shedding followed by strong virus neutralizing antibody responses, in the absence of clinical illness. All four of the subcutaneously inoculated AGMs became infected (mean peak viremia: 2.9 log 10 PFU/mL, mean duration: 4.3 days) and vRNA was detected in their oral swabs, with infectious virus being detected in a subset of these specimens. Although all four of the intravaginally inoculated AGMs developed virus neutralizing antibody responses, only three had detectable viremia (mean peak viremia: 4.0 log 10 PFU/mL, mean duration: 3.0 days). These three AGMs also had vRNA and infectious virus detected in both oral and vaginal swabs. Two of the four intrarectally inoculated AGMs became infected (mean peak viremia: 3.8 log 10 PFU/mL, mean duration: 3.5 days). vRNA was detected in oral swabs collected from both of these infected AGMs, and infectious virus was detected in an oral swab from one of these AGMs. Notably, vRNA and infectious virus were detected in vaginal swabs collected from the infected female AGM (peak viral load: 7.5 log 10 copies/mL, peak titer: 3.8 log 10 PFU/mL, range of detection: 5-21 days post infection). Abnormal clinical chemistry and hematology results were detected and acute lymphadenopathy was observed in some AGMs. Infection dynamics in all three AGM ZIKV models are similar to those reported in the PLOS NEGLECTED TROPICAL DISEASES

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Zika Virus Infection in Syrian Golden Hamsters and Strain 13 Guinea Pigs

Cited by 20 publications

References 29 publications

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

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

Binding affinities of oxytocin, vasopressin and Manning compound at oxytocin and V1a receptors in male Syrian hamster brains

Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey

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