Callithrix penicillata: A feasible experimental model for dengue virus infection

Ferreira, Milene Silveira; Castro, Paulo Henrique Gomes de; Silva, Gilmara Abreu; Casseb, Samir Mansour Moraes; Júnior, Antônio Gregório Dias; Rodrigues, Sueli G.; Azevedo, Raimunda do Socorro da Silva; Silva, Matheus Fernandes Costa e; Zauli, Danielle Alves Gomes; Araújo, Márcio Sobreira Silva; Béla, Samantha Ribeiro; Teixeira-Carvalho, Andréa; Martins‐Filho, Olindo Assis; Vasconcelos, Pedro Fernando da Costa

doi:10.1016/j.imlet.2013.12.008

Cited by 22 publications

(15 citation statements)

References 21 publications

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“…In an attempt to translate these models to non‐human primates, we previously investigated the kinetics of peripheral blood biomarkers in immunocompetent Callithrix penicillata (black‐tufted marmoset) infected with DENV3; our findings demonstrated that, as previously shown in the common marmoset ( C. jacchus ), this species can provide a relevant experimental model for DENV infection for both early and late stages of the inflammatory response . Subsequently, a model for secondary DENV infection was established in C. jacchus , with high levels of viremia and serotype cross‐reactive antibody responses .…”

Section: Introductionsupporting

confidence: 52%

“…In a previous report, we demonstrated that a single intraperitoneal injection of DENV3 in C. penicillata reproduced many aspects of DENV disease, including viremia, characteristic hematological and serological cytokine profiles, and liver damage . In the present report, we tested in the same species the hypothesis that an exacerbated inflammatory response would be associated with ADE in this monkey model.…”

Section: Discussionmentioning

confidence: 56%

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Antibody‐enhanced dengue disease generates a marked CNS inflammatory response in the black‐tufted marmoset Callithrix penicillata

et al. 2015

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Severe dengue disease is often associated with long-term neurological impairments, but it is unclear what mechanisms are associated with neurological sequelae. Previously, we demonstrated antibody-enhanced dengue disease (ADE) dengue in an immunocompetent mouse model with a dengue virus 2 (DENV2) antibody injection followed by DENV3 virus infection. Here we migrated this ADE model to Callithrix penicillata. To mimic human multiple infections of endemic zones where abundant vectors and multiple serotypes co-exist, three animals received weekly subcutaneous injections of DENV3 (genotype III)-infected supernatant of C6/36 cell cultures, followed 24 h later by anti-DENV2 antibody for 12 weeks. There were six control animals, two of which received weekly anti-DENV2 antibodies, and four further animals received no injections. After multiple infections, brain, liver, and spleen samples were collected and tissue was immunolabeled for DENV3 antigens, ionized calcium binding adapter molecule 1, Ki-67, TNFα. There were marked morphological changes in the microglial population of ADE monkeys characterized by more highly ramified microglial processes, higher numbers of trees and larger surface areas. These changes were associated with intense TNFα-positive immunolabeling. It is unclear why ADE should generate such microglial activation given that IgG does not cross the blood-brain barrier, but this study reveals that in ADE dengue therapy targeting the CNS host response is likely to be important.

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Section: Introductionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 56%

Antibody‐enhanced dengue disease generates a marked CNS inflammatory response in the black‐tufted marmoset Callithrix penicillata

et al. 2015

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“…It is known that ZIKV infection of rhesus and cynomolgus monkeys recapitulates many key clinical findings, including rapid clearance of acute viremia, early invasion of the CNS, and prolonged viral shedding 33 , 35 – 39 . In accordance, the common marmoset is regarded as a feasible experimental model for the study of arboviral infections such as DENV 40 because they can be easily kept in captivity owing to their the small size and the lower maintenance costs 41 . In the present study, we were able to successfully infect four marmosets with a low passage clinical isolate of ZIKV (HS-2015-BA-01) from a viremic patient with symptomatic ZIKV infection in Bahia State/Brazil.…”

Section: Discussionmentioning

confidence: 99%

Evidence of natural Zika virus infection in neotropical non-human primates in Brazil

Terzian

Zini

Sacchetto

et al. 2018

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In Africa, Old World Primates are involved in the maintenance of sylvatic circulation of ZIKV. However, in Brazil, the hosts for the sylvatic cycle remain unknown. We hypothesized that free-living NHPs might play a role in urban/periurban ZIKV dynamics, thus we undertook an NHP ZIKV investigation in two cities in Brazil. We identified ZIKV-positive NHPs and sequences obtained were phylogenetically related to the American lineage of ZIKV. Additionally, we inoculated four C. penicillata with ZIKV and our results demonstrated that marmosets had a sustained viremia. The natural and experimental infection of NHPs with ZIKV, support the hypothesis that NHPs may be a vertebrate host in the maintainance of ZIKV transmission/circulation in urban tropical settings. Further studies are needed to understand the role they may play in maintaining the urban cycle of the ZIKV and how they may be a conduit in establishing an enzootic transmission cycle in tropical Latin America.

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“…In addition, several potential dengue biomarkers, such as creatine phosphokinase (CK), TNF-alpha, IFM gamma, IL-8 and IL10, have been observed in NHPs following DENV inoculation [19,45,50,66]. Marmosets exhibited elevated levels of TGF-α and IFN-γ during the early phase of DENV infection and demonstrated altered serum biochemical, thrombocytopenia and leukopenia [13,20,21,50]. Marmosets with secondary DENV infection demonstrated infectious virus-immune complex and higher viremia titers, as detected by using Fc gamma receptor expressing cells.…”

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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Callithrix penicillata: A feasible experimental model for dengue virus infection

Cited by 22 publications

References 21 publications

Antibody‐enhanced dengue disease generates a marked CNS inflammatory response in the black‐tufted marmoset Callithrix penicillata

Antibody‐enhanced dengue disease generates a marked CNS inflammatory response in the black‐tufted marmoset Callithrix penicillata

Evidence of natural Zika virus infection in neotropical non-human primates in Brazil

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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