Evaluation of Macaca radiata as a non-human primate model of Dengue virus infection

Kato, Fumihiro; Ishida, Yuichi; Kawakami, Akihiko; Takasaki, Tomohiko; Saijo, Masayuki; Miura, Tomoyuki; Hishiki, Takayuki

doi:10.1038/s41598-018-21582-9

Cited by 9 publications

(9 citation statements)

References 38 publications

(37 reference statements)

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“…Results from this study largely support previous findings of minimal pathologic changes following ZIKV infection of cynomolgus macaques, with a lack of weight loss or febrile response ( Figure 3 a,b) [ 62 , 66 ]. Some rectal temperatures were low during the first 12 dpi ( Figure 3 b), as previously demonstrated in immunocompromised mice infected with ZIKV [ 82 ], as well as in bonnet monkeys ( Macaca radiatata ) infected with DENV4 [ 83 ]. Hypothermia results from our study may be partially explained by the effect sedation at the time of measurement.…”

Section: Discussionsupporting

confidence: 76%

ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques

Azar

Rossi

Haller

et al. 2018

Viruses

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To evaluate the effects of ZIKV infection on non-human primates (NHPs), as well as to investigate whether these NHPs develop sufficient viremia to infect the major urban vector mosquito, Aedes aegypti, four cynomolgus macaques (Macaca fascicularis) were subcutaneously infected with 5.0 log10 focus-forming units (FFU) of DNA clone-derived ZIKV strain FSS13025 (Asian lineage, Cambodia, 2010). Following infection, the animals were sampled (blood, urine, tears, and saliva), underwent daily health monitoring, and were exposed to Ae. aegypti at specified time points. All four animals developed viremia, which peaked 3–4 days post-infection at a maximum value of 6.9 log10 genome copies/mL. No virus was detected in urine, tears, or saliva. Infection by ZIKV caused minimal overt disease: serum biochemistry and CBC values largely fell within the normal ranges, and cytokine elevations were minimal. Strikingly, the minimally colonized population of Ae. aegypti exposed to viremic animals demonstrated a maximum infection rate of 26% during peak viremia, with two of the four macaques failing to infect a single mosquito at any time point. These data indicate that cynomolgus macaques may be an effective model for ZIKV infection of humans and highlights the relative refractoriness of Ae. aegypti for ZIKV infection at the levels of viremia observed.

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Section: Discussionsupporting

confidence: 76%

ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques

Azar

Rossi

Haller

et al. 2018

Viruses

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“…The second result was used as the final result. Antibody responses were investigated using an enzyme immune assay (EIA), as per Kato et al 19 The IgM and IgG results were considered positive if there was a 4-fold rise in EIA units between days 0 and either day 14 or 28. The same cutoff was used for both DENV and JEV assays.…”

Section: Methodsmentioning

confidence: 99%

Virological and Immunological Outcomes in Rhesus Monkeys after Exposure to Dengue Virus–Infected Aedes aegypti Mosquitoes

Carrington

Ponlawat

Nitatsukprasert

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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. This study describes the natural history of dengue virus (DENV) infection in rhesus monkeys exposed to the bites of DENV-infected Aedes aegypti mosquitoes. Dengue virus–infected mosquitoes were generated by either intrathoracic inoculation or by oral feeding on viremic blood meals. Each of the six rhesus monkeys that were fed upon by intrathoracically infected mosquitoes developed non-structural protein 1 (NS1) antigenemia and an IgM response; viremia was detected in 4/6 individuals. No virological or immunological evidence of DENV infection was detected in the three monkeys exposed to mosquitoes that had been orally infected with DENV. These results demonstrate the utility of mosquito-borne challenge of rhesus monkeys with DENV.

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“…In addition, NHP models, including pigtail macaque, rhesus macaque, and owl monkey have exhibited limited levels of viremia following inoculation with clinically isolated DENV strains [18,65]. Experiments using Aotus monkeys, squirrel monkeys, cotton-top tamarins, white face monkeys, black spider monkeys, Saimiri monkeys, marmosets (Marikina geoffroyi), howler monkeys, and red spider monkeys have demonstrated the susceptibility of New World monkeys to DENV, but none of these NHPs have exhibited overt clinical manifestations [42,47,48]. In recent years, rhesus macaques have been reported to show hemorrhagic signs following intravenous DENV inoculation [45].…”

Section: Animal Models For Dengue Virus Infectionmentioning

confidence: 99%

Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys

et al. 2020

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Due to the global burden of dengue disease, a vaccine is urgently needed. One of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. Characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. Preclinical studies in vaccine development usually include parameters such as safety evaluation, induction of viremia and antigenemia, immunogenicity, and vaccine effectiveness. Although mice have been used as a model, non-human primates have an advantage over mice because of their relative similarity to humans in their genetic composition and immune responses. This review compares the viremia kinetics and antibody responses of cynomolgus macaques (Macaca fasicularis), common marmosets (Callithrix jacchus), and tamarins (Saguinus midas and Saguinus labitus) and summarize the perspectives and the usefulness along with challenges in dengue vaccine development.

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Evaluation of Macaca radiata as a non-human primate model of Dengue virus infection

Cited by 9 publications

References 38 publications

ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques

ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques

Virological and Immunological Outcomes in Rhesus Monkeys after Exposure to Dengue Virus–Infected Aedes aegypti Mosquitoes

Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys

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