the chemokine receptor ccr5, a therapeutic target for hivaids antagonists, is critical for recovery in a mouse model of japanese encephalitis趋化因子受体ccr5、治疗目标条件拮抗剂,对经济复苏至关重要的日本脑炎的小鼠模型.pdf

The Chemokine Receptor CCR5, a Therapeutic Target for HIV/AIDS Antagonists, Is Critical for Recovery in a Mouse Model of Japanese Encephalitis 1 1 1,2 Maximilian Larena , Matthias Regner , Mario Lobigs * 1 Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, The Australian National University, Canberra, Australia, 2 Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia Abstract Japanese encephalitis is a severe central nervous system (CNS) inflammatory disease caused by the mosquito-borne flavivirus, Japanese encephalitis virus (JEV). In the current study we have investigated the immune responses against JEV in mice lacking expression of the chemokine receptor CCR5, which functions in activation and chemotaxis of leukocytes during infection. We show that CCR5 serves as a host antiviral factor against Japanese encephalitis, with CCR5 deficiency markedly increasing mortality, and viral burden in the CNS. Humoral immune responses, which are essential in recovery from JEV infection, were of similar magnitude in CCR5 sufficient and deficient mice. However, absence of CCR5 resulted in a multifaceted deficiency of cellular immune responses characterized by reduced natural killer and CD8+ T cell activity, low splenic cellularity, and impaired trafficking of leukocytes to the brain. Interestingly, adoptive transfer of immune spleen cells, depleted of B lymphocytes, increased resistance of CCR5-deficient recipient mice against JEV regardless of whether the cells were obtained from CCR5-deficient or wild-type donor mice, and only when transferre