Tracking genetic changes in West Nile Virus that could affect its spread and the ability of blood donor screening tests, future treatments, and vaccines to work effectively
Scientists at the US Food and Drug Administration (FDA) have gained important insights into understanding the genetic changes the mosquito-borne West Nile Virus (WNV) acquired since it emerged in the United States in 1999.
West Nile virus (WNV) is usually passed between infected mosquitoes and birds. However, mosquitoes occasionally infect humans, causing symptoms in about 20% of those individuals. Symptoms can resemble mild, flulike illness, although rarely (~1% of infections), the virus can invade the nervous system, causing meningitis (inflammation of the brain membranes), encephalitis (inflammation of the brain), or paralysis.
The FDA study is important because it highlights the need for continuously tracking and identifying new genetic variants of WNV in order to protect public health from the annual outbreak of this disease, for which there are no specific therapies or vaccines. The virus can be transmitted by transfusion of blood and blood components and by organ transplantation. Moreover, tests used to diagnose infection and screen blood donors, as well as vaccines and drug therapies currently in development, may not perform as well against newer genetic variants of WNV.
In order to study the evolution of WNV in the US since 1999, the FDA scientists analyzed the genes of viruses isolated from samples of blood donated by 19 human donors who tested positive for the infection during the 2012 US outbreak. They also examined previously identified sequences of WNV genes from samples obtained from 1999–2012. A genetic sequence is the order of building blocks making up a specific gene. Analyzing sequences enables scientists to identify mutations and study how an organism is evolving over time.
The scientists detected several codons in the WNV genetic material that had undergone mutations that remained in a variety of virus populations over the years. Codons are sections of genes that code for amino acids, the building blocks of proteins.
The study found that from 1999 to 2008, mutations regularly occurred in WNV populations around the US, causing genetic divergence; that is, various populations of the virus accumulated different patterns of mutations, creating genetically distinct groups of the virus. Then, following a brief halt during 2008–2009, genetic divergence resumed up to and including the outbreak in 2012. Overall, this study suggests that the patterns of WNV genetic evolution in the U.S. following the 2012 outbreak remained consistent with previous trends identified by other researchers.
Importantly, there were still some closely related genetic variants of the virus across a broad area of the US during the 2012 outbreak, which was the largest since 2003, causing 5,674 cases and 286 deaths. Based on previous research by others, the discovery of widespread occurrence of genetically similar variants in the FDA study suggests that migratory birds might have spread them over this broad area.
The study’s findings also suggest that these genetically similar variants may be a new strain of WNV emerging in the United States. They also suggest that by studying genetic changes in the virus, scientists can obtain important insights into the virus’s ability to spread, clues for designing anti-WNV vaccines, drug treatments, and reliable tests for screening blood donors for this virus.
Genetic Variability of West Nile Virus in U.S. Blood Donors from the 2012 Epidemic Season
PLOS Neglected Tropical Diseases
2016 May; 10(5): doi:10.1371/journal.pntd.0004717
Andriyan Grinev1*, Caren Chancey1, Evgeniya Volkova1, Germán Añez1¤a, Daniel A.
R. Heisey1¤b, Valerie Winkelman2, Gregory A. Foster3, Phillip Williamson2, Susan
L. Stramer3, Maria Rios1*
1 Laboratory of Emerging Pathogens (LEP), Division of Emerging and Transfusion Transmitted Diseases
(DETTD), Office of Blood Research and Review (OBRR), Center for Biologics Evaluation and Research
(CBER), Food and Drug Administration (FDA), Silver Spring, Maryland, United States of America, 2Creative
Testing Solutions, Tempe, Arizona, United States of America, 3American Red Cross, Gaithersburg,
Maryland, United States of America
a Current address: Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America
b Current address: Virginia Commonwealth University, Richmond, Virginia, United States of America