Susceptibility to West Nile Virus Infection

West Nile virus (WNV) is a mosquito-borne RNA virus that poses a significant clinical problem across the globe. Control of the infection is complicated by the fact that no vaccine against WNV infection is available. While most West Nile virus infections are asymptomatic, the virus occasionally causes severe neurological disease and even death in some patients. Indeed, current statistics indicate that the virus is responsible for 1500 deaths in the United States between 1999 and 2012. Although age is a major risk factor for severe disease, other susceptibility factors are incompletely defined. In this regard, the current issue of Viral Immunology features a very interesting article that identifies immune markers associated with host susceptibility to infection with West Nile virus. Qian et al. have profiled immune markers from a cohort of 102 healthy subjects with a history of asymptomatic or severe infection with WNV. The authors show that subjects with a history of severe infection had significantly lower levels of serum IL-4, and that these changes in IL-4 levels were associated with altered gene expression patterns in PBMCs. The authors also identified a set of genes that exhibited altered expression levels in individuals with a history of asymptomatic or severe infection. The hope is that the data will lead to a better understanding of immune control of WNV and new approaches to identifying individuals at risk for more severe disease. This will be an important step forward in controlling this viral infection.

Other articles in this issue address several different aspects of the host response to viral infections. Painter et al. have analyzed the humoral response to influenza A virus infection in older adults. Using a B cell ELISPOT assay to measure virus-specific B cells after influenza vaccination in older adults, the authors have characterized kinetics of the response in detail. The results suggest that the B cell ELISPOT assay is an excellent tool to profile and monitor the humoral immune responses in older subjects after influenza vaccination. An article by Nazmi and colleagues investigates the role of neural stem/progenitor cells (NSPCs) in the immune response. Using a model of Japanese encephalitis virus (JEV), the authors show that NSPCs regulate excessive inflammation in the CNS by converting encephalitogenic T-cells into CD4+CD25+FOXP3+regulatory T cells. This conversion was dependent on direct contact between the T-cells and the NSPCs. The study offers new insights into the interaction between CNS-infiltrating encephalitogenic T-cells and NSPCs during viral encephalitis. Seo and Hahm have investigated the effect of a sphingosine analog, AAL-R, on the activation of dendritic cells (DCs) infected with lymphocytic choriomeningitis virus (LCMV). Interestingly, AAL-R increased type I IFN production from DCs infected with LCMV, suggesting that the sphingosine analog acted directly on DCs to promote defensive responses via type I IFN signaling.

Two studies focus on technical issues related to vaccination and protein production. Ferreira de Lima Neto and colleagues have investigated the effect of high hydrostatic pressure (HHP) on tobacco mosaic virus (TMV). Using a mouse model of infection, the authors show that HHP significantly altered the recognition epitopes when compared to the native virus. Importantly, different cleavage sites were exposed after treatments and this was confirmed by epitope mapping studies. The data suggest that HHP can be used to prepare whole virus particles that are highly immunogenic and still retain neutralizing epitopes, in addition to unmasking other epitopes that are normally unavailable in the native virus before treatment. Abdel-Moneim et al. have engineered dual expression vectors containing the N and S proteins of avian infectious bronchitis virus. The genes are under the control of human and murine cytomegalovirus immediate-early enhancer/promoter elements in combination with the baculoviral polyhedrin and p10 promoters to allow for simultaneous expression in both vertebrate and insect cells. The studies show that the dual expression cassettes yielded high levels of protein from both transcription units. These vectors will be invaluable for the production of large quantities of purified proteins.