title: A hamster-derived West Nile virus isolate induces persistent renal infection in mice.
abstract: BACKGROUND
  West Nile virus (WNV) can persist long term in the brain and kidney tissues of humans, non-human primates, and hamsters. In this study, mice were infected with WNV strain H8912, previously cultured from the urine of a persistently infected hamster, to determine its pathogenesis in a murine host.
  
  
  RESULTS
  We found that WNV H8912 was highly attenuated for neuroinvasiveness in mice. Following a systemic infection, viral RNA could be detected quickly in blood and spleen and much later in kidneys. WNV H8912 induced constitutive IL-10 production, upregulation of IFN-β and IL-1β expression, and a specific IgM response on day 10 post-infection. WNV H8912 persisted preferentially in kidneys with mild renal inflammation, and less frequently in spleen for up to 2.5 months post infection. This was concurrent with detectable serum WNV-specific IgM and IgG production. There were also significantly fewer WNV- specific T cells and lower inflammatory responses in kidneys than in spleen. Previous studies have shown that systemic wild-type WNV NY99 infection induced virus persistence preferentially in spleen than in mouse kidneys. Here, we noted that splenocytes of WNV H8912-infected mice produced significantly less IL-10 than those of WNV NY99-infected mice. Finally, WNV H8912 was also attenuated in neurovirulence. Following intracranial inoculation, WNV persisted in the brain at a low frequency, concurrent with neither inflammatory responses nor neuronal damage in the brain.
  
  
  CONCLUSIONS
  WNV H8912 is highly attenuated in both neuroinvasiveness and neurovirulence in mice. It induces a low and delayed anti-viral response in mice and preferentially persists in the kidneys.
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Vandana
authors.initials: V
authors.lastname: Saxena
authors.forename: Guorui
authors.initials: G
authors.lastname: Xie
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.forename: Tierra
authors.initials: T
authors.lastname: Farris
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.forename: Bin
authors.initials: B
authors.lastname: Gong
authors.forename: Paul
authors.initials: P
authors.lastname: Boor
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Tang
authors.forename: Robert
authors.initials: R
authors.lastname: Tesh
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000825:Animal Structures / Q000821:virology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002908:Chronic Disease; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D014901:West Nile Fever / Q000473:pathology / Q000821:virology*; D014902:West Nile virus / Q000302:isolation & purification* / Q000472:pathogenicity
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012367:RNA, Viral