title: Met-CCL5 represents an immunotherapy strategy to ameliorate rabies virus infection.
abstract: BACKGROUND
  Infection of rabies virus (RABV) causes central nervous system (CNS) dysfunction and results in high mortality in human and animals. However, it is still unclear whether and how CNS inflammation and immune response contribute to RABV infection.
  
  
  METHODS
  Suckling mice were intracerebrally infected with attenuated RABV aG and CTN strains, followed by examination of chemokine or cytokine production, inflammatory cell infiltration and neuron apoptosis in the brain. Furthermore, the suckling mice and adult mice that were intracerebrally infected with aG and the adult mice that were intramuscularly infected with street RABV HN10 were treated with CCL5 antagonist (Met-CCL5) daily beginning on day 2 postinfection. The survival rates and inflammation responses in the CNS of these mice were analyzed.
  
  
  RESULTS
  Excessive CCL5 in the CNS was associated with CNS dysfunction, inflammation, and macrophage or lymphocyte infiltration after attenuated or street RABV infection. Administration of exogenous CCL5 induced excessive infiltration of immune cells into the CNS and enhanced inflammatory chemokine and cytokine production. Met-CCL5 treatment significantly prolonged survival time of the suckling mice inoculated with aG and adult mice infected with aG and HN10.
  
  
  CONCLUSIONS
  These results suggest that CCL5 in the CNS is a key regulator involved in inducing rabies encephalomyelitis. Furthermore, treatment with the CCL5 antagonist Met-CCL5 prolongs survival time of the mice infected with attenuated or street RABVs, which might represent a novel therapeutic strategy to ameliorate RABV infection.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Shaozhuo
authors.initials: S
authors.lastname: Jiao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tao
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.forename: Wentao
authors.initials: W
authors.lastname: Jiao
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guodong
authors.initials: G
authors.lastname: Liang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000276:immunology / Q000628:therapy*; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors*; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D011818:Rabies / Q000276:immunology / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5