Zika virus has undergone significant genetic changes in the past few decades, analysis finds

John Murphy, MDLinx | April 19, 2016

Researchers who performed a detailed genetic analysis on the Zika virus have found some clues to help explain how the virus evolved from causing a relatively benign illness to becoming a worldwide threat, according to a study published online April 15, 2016 in the journal Cell Host & Microbe.

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Zika virus evolved with genetic changes

Genetic mutations in the Zika virus (in green, as it infects neural cells, in gray) could cause it to replicate more efficiently, evade the body’s immune response or invade new tissues, researchers reported. (Image: Sarah C. Ogden, Florida State University)

“The Zika virus has undergone significant genetic changes in the past 70 years,” said the study's senior author Genhong Cheng, PhD, a Professor of Microbiology, Immunology, and Molecular Genetics at the University of California at Los Angeles David Geffen School of Medicine, in Los Angeles, CA.

Investigators have speculated that Zika virus may have evolved only in recent years to become more neurotropic, better at replicating, and more transmissible to humans. The latest epidemic has linked the virus to fetal brain-development disorders and new modes of transmission, including infection through sexual contact and from mother to fetus.

“We don’t know why Zika infection was not associated with serious human disease, especially in newborns, until recently,” said co-author Stephanie Valderramos, MD, PhD, a fellow in Maternal-Fetal Medicine at the Geffen School. “We hoped that taking a closer look at the virus’ genetic changes over time would reveal clues to this mystery.”

To understand the molecular evolution of the virus, the researchers performed detailed phylogenetic and genetic analyses, as well as targeted structural modeling, on all known strains of Zika virus, with an emphasis on the recent human strains.

“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,” Dr. Cheng said.

Along with researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, Dr. Cheng and colleagues compared individual genetic differences among 41 strains of Zika virus—30 isolates from humans, 10 from mosquitoes, and 1 from monkeys. 

In sequencing the virus, the team identified substantial DNA changes between the strains, showing a major split between the Asian and African lineages, as well as the human and mosquito versions. 

Interestingly, the researchers found that the human strains share a genetic sequence more similar to the 1966 Malaysian strain than the 1968 Nigerian strain, which suggests that the Zika virus strains in the recent human outbreak are evolved from the Asian lineage.

The researchers also found a key viral protein that varied the most between the Asian human strain and the African mosquito strain. This indicates that the virus likely underwent a structural change at some point.

“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,” said co-author Lulan Wang, a graduate student researcher in Dr. Cheng’s laboratory.

The researchers’ next step will be to analyze the viral strains causing the current epidemic and look for genetic targets for drug and vaccine development.

“Our results have raised new questions about the evolution of the Zika virus, and highlight that a lot more research is needed to understand the relationship between the virus and human disease,” Dr. Cheng said.

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