Reaction Rights and Wrongs
Research into patient response to West Nile virus has uncovered some unexpected results...
Michael Schubert |
Every few years, the mosquito finds itself in the news for its impressive ability to transmit pathogens to humans. Though the list of mosquito-borne diseases is a long one that includes malaria, encephalitis and the currently infamous Zika virus, one that regularly makes its presence known is West Nile virus (WNV). This flavivirus, although asymptomatic in about 80 percent of those infected, causes flu-like symptoms in others – and worse, one in 150 patients experiences severe neuroinvasive disease with a fatality rate of about 10 percent (1). But what makes some patients respond poorly to infection, while others experience no symptoms at all? Eddie James and his colleagues at the Benaroya Research Institute at Virginia Mason Medical Center thought the answer might lie in patients’ immune responses.
“This was actually a case where our initial results were not what we expected,” James says. “Several of our first subjects with severe infections were elderly and we expected them to have impaired T cell responses, but instead we saw the opposite – many more WNV-specific T cells and a more functional response. That observation led us to a new hypothesis that the virus was triggering exaggerated immune responses and causing problems in subjects who had worse outcomes.” The researchers compared blood samples from 24 donors with asymptomatic infections and 16 with neuroinvasive disease (2). Patients in the latter group had higher numbers of WNV-specific CD4+ T cells, which are crucial for viral protection and clearance from the central nervous system. Not only that, but the cells behave differently to those of asymptomatic individuals.
The information has applicability beyond WNV. “In an earlier publication on H1N1 infections (3), we noticed that subjects hospitalized due to influenza infection had exaggerated influenza responses. In cases like that, it could be beneficial in some cases to use low-dose steroids or more targeted drugs to dampen the immune response.” The team hope to explore the issue further using more common viruses, like influenza, as a model system to find out whether the potential for exaggerated response can be detected beforehand – and perhaps one day lead to a clinical test.
- WebMD, “West Nile Virus Questions Answered”. Available at: wb.md/1S4g3au. Accessed March 16, 2016.
- EA James et al., “Neuroinvasive West Nile infection elicits elevated and atypically polarized T cell responses that promote a pathogenic outcome”, PLoS Pathog, 12, e1005375 (2016). PMID: 26795118.
- J Yang et al., “CD4+ T cells recognize unique and conserved 2009 H1N1 influenza hemagglutinin epitopes after natural infection and vaccination”, Int Immunol, 25, 447–457 (2013).