title: Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for secondary dengue virus infection: high levels of viraemia and serotype cross-reactive antibody responses consistent with secondary infection of humans.
abstract: There are four dengue virus (DENV) serotypes. Primary infection with one does not confer protective immunity against the others. We have reported previously that the marmoset (Callithrix jacchus) is a useful primary DENV infection model. It has been reported that secondary DENV infection with a heterotypic serotype induces viraemia kinetics and antibody responses that differ from those in primary infection. Thus, it is important to determine the utility of the marmoset as a model for secondary DENV infection. Marmosets were infected with heterologous DENV by secondary inoculation, and viraemia kinetics and antibody responses were analysed. The marmosets consistently developed high levels of viraemia after the secondary inoculation with heterologous DENV serotypes. IgM responses were lower compared with primary inoculation responses, whilst IgG responses were rapid and high. Neutralizing activities, which possessed serotype cross-reactive activities, were detected as early as 4 days after inoculation. In addition, infectious viraemia titres were higher when assayed with Fcγ receptor-expressing baby hamster kidney (BHK) cells than when assayed with conventional BHK cells, suggesting the presence of infectious virus-antibody immune complexes. After secondary infection with heterotypic DENV, the marmosets demonstrated viraemia kinetics, IgM and IgG responses, and high levels of serotype cross-reactive neutralizing antibody responses, all of which were consistent with secondary DENV infection in humans. The results indicate the marmoset as a useful animal for studying secondary, as well as primary, DENV infection.
authors: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Meng Ling
authors: ML
authors: Moi
authors: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Tomohiko
authors: T
authors: Takasaki
authors: Research and Education Center for Prevention of Global Infectious Diseases of Animals, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
authors: Tsutomu
authors: T
authors: Omatsu
authors: Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors: Shinichiro
authors: S
authors: Nakamura
authors: Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki, Japan.
authors: Yuko
authors: Y
authors: Katakai
authors: Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Yasushi
authors: Y
authors: Ami
authors: Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Yuriko
authors: Y
authors: Suzaki
authors: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Saijo
authors: Section of Comparative Immunology and Microbiology, Center for Human Evolution Modeling Research Institute, Kyoto University, Inuyama, Aichi, Japan.
authors: Hirofumi
authors: H
authors: Akari
authors: National Institute of Infectious Diseases, Tokyo, Japan.
authors: Ichiro
authors: I
authors: Kurane
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D002144:Callithrix / Q000276:immunology / Q000821:virology; D002460:Cell Line; D060085:Coinfection / Q000276:immunology* / Q000821:virology; D006224:Cricetinae; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D014766:Viremia / Q000276:immunology* / Q000821:virology
chemical_list: D000914:Antibodies, Viral