As part of ongoing efforts to learn more about the Zika virus, researchers from the MRC-University of Glasgow Centre for Virus Research in the United Kingdom and the Fundacao Oswaldo Cruz-PE/Centro de Pesquisas Aggeu Magalhaes in Recife, Brazil, isolated the full-length genome sequence, including non-coding regions, of the mosquito-borne infection, potentially providing the building blocks upon which to build genetic tools to prevent and/or treat the disease.
In a paper
published on October 5 by the journal PLOS Neglected Tropical Diseases
, a research team reported using a Zika virus isolate—PE243—from a patient in Brazil, where the virus has been a public health challenge since 2014. The isolate was obtained via amplification in C6/36 Aedes albopictus
cells and Vero cells. Using high-throughput sequencing and other technologies, the researchers report that they identified a subgenomic flavivirus RNA (sfRNA) in Zika cells. Interestingly, the interferon induction assays they performed suggest that Zika virus sfRNA “may have broader antagonist activity compared to Dengue virus sfRNA, which may contribute to disease outcome.”
As the authors note, earlier studies have shown that most American isolates of Zika are genetically comparable, with roughly 99% homology at the nucleotide level. Their isolate is most similar to the Brazilian isolate ZikaSPH2015 (99.9% homology at the nucleotide level and 99.97% homology at amino acid level).
In their analysis, PE243 was susceptible to type I interferon responses—with the isolate’s sfRNA reducing activation of interferon-β promoter to levels similar to that found in Dengue, another mosquito-borne virus. In fact, it produced significantly larger plaque sizes in type I interferon-incompetent A549/BVDV-Npro cells than in A549 cells. This is notable, given that host interferon response is considered vital in fighting viral infection and preventing virus replication in mosquito-borne viruses such as Zika. Based on their sequencing analysis and on comparisons with the genome sequences of other flaviviruses, they were able to model the genetic structure of PE243, and they believe that the sfRNA structures of Asian and African strains of Zika are actually quite similar.
“Our sequence data for [Zika virus] PE243 and predictive analysis suggested that the sfRNA molecule begins 15 nt after the stop codon of the open reading frame and is 413 nt in length,” they wrote. “This was further confirmed by northern blot analysis, which indicates a band at the anticipated size present only in [Zika virus] PE243 infected cell lysate.”
In addition, they believe that Zika virus’ “stimulation of RIG-I results in a significant decrease in interferon-β promoter activity in the presence of both Dengue virus and Zika virus sfRNAs,” which suggests that the viruses “antagonize RIG-I mediated type I interferon induction.”
In their concluding remarks, they note, “The factors involved in the emergence of [Zika] from a rarely detected pathogen to a major epidemic are yet to be determined and could include genetic adaptation, environmental influences, interactions with other pathogens within infected individuals and changes in population dynamics of the virus. It has been suggested that alterations in codon usage in the NS1 gene may have facilitated an adaptation towards improved fitness for human infections in the Asian lineage over the African. These changes, combined with the geographical ranges throughout the Americas of its vector population, may have contributed to [Zika’s] accelerated spread. In order to understand not only [Zika’s] evolution and pathogenesis but also to support the development of virus-based tools, it is imperative to generate full virus genome sequences from isolates in the Americas and elsewhere associated with classical and non-classical symptoms.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.
To stay informed on the latest in infectious disease news and developments, please sign up for our weekly newsletter.