A Hamster-Derived West Nile Virus Isolate Induces Persistent Renal Infection in Mice

Vandana Saxena, Guorui Xie, Bei Li, Tierra Farris, Thomas Welte, Bin Gong, Paul Boor, Ping Wu, Shao-Jun Tang, Robert Tesh, Tian Wang

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.Methodology/Principal Findings: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.

Original languageEnglish (US)
Article numbere2275
JournalPLoS Neglected Tropical Diseases
Volume7
Issue number6
DOIs
StatePublished - Jun 2013

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West Nile virus
Cricetinae
Kidney
Infection
Spleen
Interleukin-10
Immunoglobulin M
Brain
Viral RNA
Virus Diseases
Interleukin-1
Primates

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Medicine(all)

Cite this

A Hamster-Derived West Nile Virus Isolate Induces Persistent Renal Infection in Mice. / Saxena, Vandana; Xie, Guorui; Li, Bei; Farris, Tierra; Welte, Thomas; Gong, Bin; Boor, Paul; Wu, Ping; Tang, Shao-Jun; Tesh, Robert; Wang, Tian.

In: PLoS Neglected Tropical Diseases, Vol. 7, No. 6, e2275, 06.2013.

Research output: Contribution to journalArticle

Saxena, Vandana ; Xie, Guorui ; Li, Bei ; Farris, Tierra ; Welte, Thomas ; Gong, Bin ; Boor, Paul ; Wu, Ping ; Tang, Shao-Jun ; Tesh, Robert ; Wang, Tian. / A Hamster-Derived West Nile Virus Isolate Induces Persistent Renal Infection in Mice. In: PLoS Neglected Tropical Diseases. 2013 ; Vol. 7, No. 6.
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