Human neural progenitor cells (gray) infected with Zika virus (green) increased the enzyme caspase-3 (red), suggesting increased cell death.
“The Zika virus has undergone significant genetic changes in the past 70 years,” says Genhong Cheng, PhD, professor of microbiology, immunology and molecular genetics. “By tracing its genetic mutations, we aimed to understand how the virus is transmitted from person to person and how it causes different types of disease.”
First isolated in 1947, the Zika virus only sporadically caused disease in Africa and Asia until the 2007 Micronesia and 2013 French Polynesia outbreaks. Scientists previously believed that infection was spread solely by mosquitoes and caused only mild illnesses. The latest epidemic, which has drawn international attention, has linked the virus to fetal brain-development disorders and Guillain-Barre syndrome. New modes of transmission, including sexual intercourse, also have surfaced.
“We don’t know why Zika infection was not associated with serious human disease, especially in newborns, until recently,” says Stephanie Valderramos, MD (FEL ’16), PhD, a specialist in maternal-fetal health. “We hoped that taking a closer look at the virus's genetic changes over time would reveal clues to this mystery.”
Dr. Cheng’s laboratory collaborated with researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, to compare individual genetic differences among 41 strains of Zika. Thirty strains originated from humans, 10 from mosquitoes and one from monkeys. In sequencing the virus, the team identified substantial nucleotide changes between the strains, showing a major split between the Asian and African lineages, as well as the human and mosquito versions. “We suspect these mutations could help the virus replicate more efficiently, evade the body’s immune response or invade new tissues that provide a safe harbor for it to spread,” says Lulan Wang, a PhD-student researcher in Dr. Cheng’s laboratory.
The study also found that contemporary human strains of Zika share a genetic sequence more similar to the 1966 Malaysian strain than the 1968 Nigerian strain. This implies the strains causing the current human outbreak evolved from the Asian lineage. Additionally, researchers discovered human strains in the current epidemic resemble the 2013 French Polynesia strain more closely than the 2007 Micronesia strain, suggesting that the two strains evolved from a common viral ancestor. Finally, scientists determined that a key viral protein varied the most between the Asian human strain and the African mosquito strain, indicating a possible structural change in the virus.
“Our results have raised new questions about the evolution of the Zika virus,” Dr. Cheng says, “and highlight that a lot more research is needed to understand the relationship between the virus and human disease.”
“From Mosquitos to Humans: Genetic Evolution of Zika Virus,” Cell Host & Microbe, May 11, 2016