title: Infant mouse brain passaged Dengue serotype 2 virus induces non-neurological disease with inflammatory spleen collapse in AG129 mice after splenic adaptation.
abstract: AG129 mice are known to be permissive to infection by multiple serotypes of Dengue virus (DENV). There exists a concern that mouse passaged strains of the virus may induce neurological complications rather than increased vascular permeability in these mice, hence the use of human clinical isolates of the virus to develop the AG129 mouse model of Dengue disease with increased vascular permeability. The present study evaluated four mouse brain passaged DENV strains, each belonging to a different serotype and three of them having an original isolation history in India, for their suitability to serve as candidates to induce rapid lethal disease in AG129 mice. While all the viruses were able to establish a productive infection in the spleen, none of them induced paralysis despite their mouse brain passage history. Only the type-2 virus acquired the ability to induce a lethal disease after a single round of spleen to spleen passage, and became highly virulent after five more rounds. This apparently non-neurological lethal disease was characterized by high viral burden, elevated vascular permeability, serum TNF-α surge immediately before moribund stage, transient leukocytosis followed by severe leukopenia, lymphopenia throughout the course of the infection, and transient thrombocytopenia. The disease was also characterized by inflammatory splenic collapse during moribund stage, reminiscent of spontaneous splenic rupture reported in rare cases of severe Dengue in humans.
authors: Therapeutic proteins Group, Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt Ltd., Rabale, Navi Mumbai 400 701, Maharashtra, India.
authors: Yogesh
authors: Y
authors: Rajmane
authors: Sameer
authors: S
authors: Shaikh
authors: Khalander
authors: K
authors: Basha
authors: G E C Vidyadhar
authors: GE
authors: Reddy
authors: Soumya
authors: S
authors: Nair
authors: Sangita
authors: S
authors: Kamath
authors: Greeshma
authors: G
authors: Sreejesh
authors: Harinarayana
authors: H
authors: Rao
authors: Venkata
authors: V
authors: Ramana
authors: A S Manoj
authors: AS
authors: Kumar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000821:virology*; D002199:Capillary Permeability; D003715:Dengue / Q000473:pathology* / Q000821:virology*; D003716:Dengue Virus / Q000302:isolation & purification / Q000472:pathogenicity*; D004195:Disease Models, Animal; D006801:Humans; D007194:India; D007964:Leukocytosis; D051379:Mice; D010264:Paraplegia; D013154:Spleen / Q000473:pathology* / Q000821:virology; D016019:Survival Analysis; D013921:Thrombocytopenia; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019562:Viral Load
chemical_list: D014409:Tumor Necrosis Factor-alpha