title: Influence of antibodies and T cells on dengue disease outcome: insights from interferon receptor-deficient mouse models.
abstract: Dengue virus (DENV) is a globally important mosquito-borne virus that causes a spectrum of diseases ranging from dengue fever (DF) to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), affecting 3.6 billion people in 128 countries [1,2(•)]. There is an urgent need for a drug or vaccine against DENV, yet none are presently available. In fact, results from recent Phase IIb and III trials of an attenuated tetrameric vaccine revealed that the vaccine provided limited protection against DENV serotype 2 in DENV-immune people, and no protection against any serotype in naïve individuals [3-5], highlighting the difficulties associated with dengue vaccine development. A challenge in the development of a DENV vaccine is that a vaccine must protect against all four DENV serotypes, which co-circulate in endemic areas. Further complicating DENV vaccine development is that the correlates of protection are not fully defined, mechanisms regulating the generation of protective antibody and T cell responses against all four DENV serotypes are as yet to be deciphered, and the adaptive immune response may actually contribute to severe disease. Recent studies using the only available animal model of DHF/DSS in mice lacking one or more components of the interferon (IFN) system have begun to provide crucial insights into the protective versus pathogenic nature of both antibody and T cell responses to DENV. Herein, we highlight key studies using the IFN receptor-deficient mouse models toward understanding the contribution of antibodies and T cells in impacting the outcome of DENV infection.
authors.affiliation: La Jolla Institute for Allergy & Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Tang
authors.affiliation: La Jolla Institute for Allergy & Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Rajvir
authors.initials: R
authors.lastname: Grewal
authors.affiliation: La Jolla Institute for Allergy & Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. Electronic address: sujan@liai.org.
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D017471:Receptors, Interferon