Mutational Pressure in Zika Virus: Local ADAR-Editing Areas Associated with Pauses in Translation and Replication

Abstract

Zika virus (ZIKV) spread led to the recent medical health emergency of international concern. Understanding the variations in virus system is of utmost need. Using available complete sequences of ZIKV we estimated directions of mutational pressure along the length of consensus sequences of three lineages of the virus. Results showed that guanine usage is growing in ZIKV RNA plus strand due to adenine to guanine transitions, while adenine usage is growing due to cytosine to adenine transversions. Especially high levels of guanine have been found in two-fold degenerated sites of certain areas of RNA plus strand with high amount of secondary structure. The usage of cytosine in two-fold degenerated sites shows direct dependence on the amount of secondary structure in 52% (consensus sequence of East African ZIKV lineage)—32% (consensus sequence of epidemic strains) of the length of RNA minus strand. These facts are the evidences of ADAR-editing of both strands of ZIKV genome during pauses in replication. RNA plus strand can also be edited by ADAR during pauses in translation caused by the appearance of groups of rare codons. According to our results, RNA minus strand of epidemic ZIKV strain has lower number of points in which polymerase can be stalled (allowing ADAR-editing) compared to other strains. The data on preferable directions of mutational pressure in epidemic ZIKV strain is useful for future vaccine development and understanding the evolution of new strains.

Explaining Pathogenicity of Congenital Zika and Guillain–Barré Syndromes: Does Dysregulation of RNA Editing Play a Role?

“…Our recent comparative work revealed a distinct ADAR editing signature in viral genomes, including ZIKV, suggesting that host ADAR editing plays a role in the molecular evolution of ZIKV . Our findings were corroborated by an independent evolutionary study that used a different approach from ours to identify ADAR editing footprints in ZIKV genomes. Together, these results indicate that ADAR editing is active during ZIKV infection.…”

RNA editing by the host ADAR system affects the molecular evolution of the Zika virus

“…At this time, we favor the argument that the primary substrate of ADAR editing is the double-stranded RNA intermediates that form during viral replication and transcription rather than the doublestranded stems of their folded RNA secondary structure (Carpenter et al, 2009;Khrustalev, Khrustaleva, Sharma, & Giri, 2017). This preference is based on the fact that GA is enriched to a greater degree than its complement (UC) on the positive strands of both ZIKV and DMelSV ( Figure 2).…”

Translation-associated mutational U-pressure in the first ORF of SARS-CoV-2 and other coronaviruses

“…Moreover, the direction of mutational pressure may not be similar along the entire length of the genome. 11 Coronaviruses are known as slowly mutating RNA viruses since they perform proof-reading during replication 12 .…”

“…But this changed nucleotide in the RNA may affect the RNA structure, RNA interference, and codon usage bias. 11 Since its first appearance in December, 2019, four hundred full-length sequences of ORF1 of SARS-CoV-2 have become available on GenBank. In this study, a comparative analysis of ORF1a and ORF1b has been carried out, taking the first isolate as the parent sequence.…”