Characterization of non-lethal West Nile Virus (WNV) infection in horses: Subclinical pathology and innate immune response.

The research paper in focus investigated the immune response to non-lethal West Nile virus (WNV) infections in horses and rabbits, with an emphasis on subclinical symptoms and the production of immune factors that minimize the disease’s severity.

Overview of the Research

• The study was mainly centered on the largely overlooked aspect of West Nile virus (WNV); that most of its infections are subclinical or non-lethal and do not result in encephalitis in humans and horses. The researchers wanted to reveal host responses during these infections in horses, and compare these responses with those found in rabbit models of subclinical WNV infection.
• The focus of existing research on WNV mainly lies in understanding the pathogenesis of the severe encephalitic disease, using mouse models. This study takes a different approach by investigating the milder, more common form of the disease.

Experimental Procedure

• The team infected 10 horses with the newly-emerging WNV strain, WNVNSW2011. This strain did not lead to neurological disease in any of the animals, a sign of a subclinical or non-lethal infection.
• The researchers also tested this strain on a group of New Zealand White rabbits by injecting the virus into their footpads.

Findings

• In both horses and rabbits, the infection led to an upregulation of type I and II interferon (IFN) in the peripheral blood leukocytes, observable prior to or at the time of viremia.
• The team detected transcript upregulation for IFNs, TNFα, IL1β, CXCL10, TLRs, and MyD88 in lymphoid tissues.
• In the brains of these animals, there was an increase in IFNα, CXCL10, TLR3, ISG15 and IRF7 mRNA levels along with evidence of mild encephalitis, but no detectable viral RNA or antigen—evidence of a strong and efficient immune response at the site of potential severe infection.
• The kinetic behavior of anti-WNV antibody response was found to be similar in both horses and rabbits, possibly due to the early IFN and cytokine responses observed in lumped leukocytes and lymphoid organs.

Implications

• This research points to the strong relevance of understanding the immune response in subclinical WNV infections, particularly the role of anti-viral interferons and other cytokines. Gaining this understanding can potentially guide more effective prevention strategies, treating therapies and potentially vaccines against WNV.
• The study also suggests that immunocompetent rabbits could serve as a valuable small-animal model for investigating non-lethal WNV infections, specifically unraveling the mechanisms preventing the progression of the disease.