Nav: Home

Immune response differences might determine severity of West Nile Virus disease

January 21, 2016

While most West Nile Virus (WNV) infections in humans are asymptomatic and go unnoticed, the virus causes serious and sometimes fatal neurologic illness in some people. A study published on January 21st in PLOS Pathogens suggests that an exaggerated and abnormal immune response contributes to the development of neurologic symptoms following West Nile virus infection.

William Kwok and Eddie James, both from the Benaroya Research Institute at Virginia Mason in Seattle, USA, and colleagues are interested in what determines the different outcomes of WNV infection, and whether differences in the immune response play a role. In this study, they compare the immune responses in samples from 24 blood donors who had earlier asymptomatic infections (confirmed by laboratory tests) with those in blood samples from 16 individuals diagnosed with WNV infections that had caused neuro-invasive disease with neurologic symptoms including confusion, tremors, seizures, paralysis, and vision loss.

Because CD4+ (helper) T cell responses have been shown to be sufficient for protection from WNV challenge (independent of B cells and CD8+ T cells) and crucial for viral clearance from the CNS, the researchers focused on the WNV-specific CD4+ T cell repertoires present in the blood samples.

They observed that older individuals had higher numbers of WNV-specific T cells. In addition, WNV-specific cell lines isolated from older individuals had a higher proportion of T cells that produced IFN-γ, and also a higher proportion that co-produced IFN-γ and IL-4 (both molecules that promote a strong immune response).

Comparing the magnitude and characteristics of WNV-specific CD4+ T cell response in individuals of similar ages with either neuroinvasive disease or asymptomatic infection, the researchers found that, independent of age, individuals with neuroinvasive disease had higher numbers of WNV-specific CD4+ T cells. In addition, those T cells that responded to the virus more frequently co-produced IFN-γ and IL-4. Moreover, the gene expression responses in CD4+ T cells stimulated with WNV differed between individuals with previous asymptomatic infection and those who had neuro-invasive WNV disease.

The researchers conclude that "individuals with neuroinvasive West Nile Virus infections have exaggerated and atypical responses to the virus". And while they acknowledge several limitations of the study, including the lack of data on the immune response close to the time of infection (the blood samples were drawn months and sometimes years after the diagnosis of WNV infection), they suggest that "immune mediated damage may indeed contribute to neurologic symptoms and pathogenic outcomes in the setting of WNV infection".
-end-
Please use this URL to provide readers access to the paper (Link goes live upon article publication): http://dx.plos.org/10.1371/journal.ppat.1005375

Authors and Affiliations:

Eddie A. James, Theresa J. Gates, Rebecca E. LaFond, Shinobu Yamamoto, Chester Ni, Duy Mai, Vivian H. Gersuk, Kimberly O'Brien, Quynh-Anh Nguyen, Brad Zeitner, Damien Chaussabel, William W. Kwok
Benaroya Research Institute at Virginia Mason, Seattle, Washington, United States of America

Marion C. Lanteri, Philip J. Norris
Blood Systems Research Institute, San Francisco, California, United States of America

Philip J. Norris
Departments of Laboratory Medicine and Medicine, University of California, San Francisco, San Francisco, California, United States of America

Uma Malhotra
Virginia Mason Medical Center, Seattle, Washington, United States of America

Uma Malhotra, William W. Kwok
Department of Medicine, University of Washington, Seattle, Washington, United States of America

Please contact plospathogens@plos.org if you would like more information.

Funding: This research was supported by the National Institute of Health Contract No: HHSN272200900043C http://www.niaid.nih.gov/researchfunding/contract/Pages/default.aspx. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: James EA, Gates TJ, LaFond RE, Yamamoto S, Ni C, Mai D, et al. (2016) Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome. PLoS Pathog 12(1): e1005375. doi:10.1371/journal.ppat.1005375

PLOS

Related West Nile Virus Articles:

West Nile virus in the New World: Reflections on 20 years in pursuit of an elusive foe
Though eradication of West Nile virus remains beyond our capability, the body of knowledge built since its arrival in the Americas in 1999 is now powering efforts to minimize its impact and prepare for the invasion of other mosquito-borne diseases.
Light pollution may be increasing West Nile virus spillover from wild birds
House sparrows infected with West Nile virus (WNV) that live in light polluted conditions remain infectious for two days longer than those who do not, increasing the potential for a WNV outbreak by about 41%.
Fifteen years of mosquito data implicate species most likely to transmit West Nile virus in Iowa
A study published this week that analyzed 15 years of mosquito surveillance data shows Iowa's western counties experience a higher abundance of the species thought to most commonly carry West Nile virus.
Mount Sinai researchers find significant delays in West Nile virus reporting
Mount Sinai researchers found significant delays in reporting human cases of West Nile virus, hampering real-time forecasting of the potentially deadly mosquito-borne disease, according to a study in the JAMA Network Open in April.
Insecticide resistance genes affect vector competence for West Nile virus
In a context of overuse of insecticides, which leads to the selection of resistant mosquitoes, it is already known that this resistance to insecticides affects interactions between mosquitoes and the pathogens they transmit.
More West Nile Virus News and West Nile Virus Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...