A team of researchers from Utah State University, Logan, has characterized the consensus genome sequences of three historically important Zika virus strains. This work is an important step towards developing antiviral therapeutic and preventive strategies against Zika, and related viruses. The research is published in Genome Announcements, a journal of the American Society for Microbiology.
“The epidemic in the Americas is potentially threatening the entire world,” said senior author Young-Min Lee, PhD, Associate Professor in the Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University. The new research, he said, will ultimately lead to stopping Zika’s spread, and preventing future outbreaks.
Previously, these researchers focused on understanding the molecular basis of viral replication and pathogenesis of the Japanese encephalitis virus, a mostly neglected but clinically important pathogen, which, like Zika, is a flavivirus. That research has provided a lot of information that will be critical to efforts to tame Zika, said Lee.
For example, the researchers had sequenced several clinically important strains of Japanese Encephalitis Virus (JEV), and had developed a “reverse genetics” system for manipulating those viruses. That system made it possible to create recombinant and mutant JEVs. That, and other tools these investigators developed for JEV can easily be adapted to use on Zika.
For example, these tools will allow them to create an attenuated Zika virus that can serve as a candidate vaccine, said Lee. The researchers can attenuate the virus by inactivating proteins that Zika uses to invade human cells.
The first of the three strains whose sequences the researchers have characterized was isolated in 1947, from a sentinel rhesus monkey in Uganda. “A sentinel animal is an animal intentionally placed in a particular environment to detect the presence of an infectious agent in the area,” said Lee. “Zika virus was discovered accidentally in the Zika forest of Uganda during a search for yellow fever virus, another flavivirus related to Zika.”
The second strain of Zika was isolated in 1966, from a pool of Aedes aegypti mosquitos in Malaysia. The third strain is responsible for the epidemic that recently swept Latin America. It was first isolated in early 2015, in Puerto Rico, and has now reached Florida, where it has begun to spread.
From this research, and from an analysis using the sequences of 29 available Zika virus genomes, the Utah team has shown that these viruses fall into two major genetic lineages. One of these is African, and the other is Asian. The latter includes both the Malaysian, and the American epidemic strain. That latter strain is derived from an ancestor of the Asian lineage.
Meanwhile, questions remain as to why the strains differentiated. Viruses face different environments in different hosts, said Lee. “The most obvious and significant challenge is the host immune response, and evasion of the host immune response is a key feature of the survival strategy. Studies are currently underway at Utah State University to examine the functional importance of the genetic variation on viral replication and pathogenesis.”
Article: Complete Genome Sequences of Three Historically Important, Spatiotemporally Distinct, and Genetically Divergent Strains of Zika Virus: MR-766, P6-740, and PRVABC-59, Sang-Im Yun, Byung-Hak Song, Jordan C. Frank, Justin G. Julander, Irina A. Polejaeva, Christopher J. Davies, Kenneth L. White, Young-Min Lee, Genome Announcements, doi: 10.1128/genomeA.00800-16, published July 2016.