An analysis comparing the individual
differences between over 40 strains of Zika virus (30 isolated from
humans, 10 from mosquitoes, and 1 from monkeys) has identified
significant changes in both amino acid and nucleotide sequences during
the past half-century. The data, published April 15 in Cell Host & Microbe,
support a strong divergence between the Asian and African lineages as
well as human and mosquito isolates of the virus, and will likely be
helpful as researchers flush out how a relatively unknown pathogen led
to the current outbreak.
The project—led by researchers at the University
of California, Los Angeles, and the Chinese Academy of Medical Sciences
& Peking Union Medical College, Beijing—builds on other viral
sequence analyses conducted over the past two months, with new
large-scale and structural comparisons. Highlights of the findings
include:
- All contemporary human Zika virus strains share a more similar sequence to the Malaysian/1966 strain than the Nigerian/1968 strain, suggesting the strains in the recent human outbreak evolved from the Asian lineage.
- All human strains identified in the 2015-2016 epidemic appear to be more closely related to the French Polynesia/2013 strain than the Micronesia/2007 strain, suggesting that the two variants evolved from a common ancestor.
- The prM (pre-membrane precursor) protein of the Zika virus had the highest percentage variability between the Asian human and the African mosquito subtypes, and modeling suggests that some of this variability contributes to a significant structural change.
"We believe these changes may, at least partially, explain
why the virus has demonstrated the capacity to spread exponentially in
the human
population in the Americas," says senior study author Genhong Cheng, a
professor in UCLA's Department of Microbiology, Immunology &
Molecular Genetics. "These changes could enable the virus to replicate
more efficiently, invade new tissues that provide protective niches for
viral propagation, or evade the immune system, leading to viral
persistence. Of course, all of these hypotheses will need to be tested
in experimental models."
Future sequencing work will likely focus on understanding
the Zika strain causing the 2015-2016 epidemic, which has yet to be
isolated from a mosquito. Cheng's group and others will also begin to
elucidate the structure of the viral proteins, which can inform drug and
vaccine design. "We hope that our work provides a strong basis that
will help the larger scientific community in accelerating Zika virus
research," he says.
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