title: 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.
authors.affiliation: Department of General Chemistry, Belarusian State Medical University Minsk, Belarus.
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Khrustalev
authors.affiliation: Laboratory of Cellular Technologies, Institute of Physiology of the National Academy of Sciences of Belarus Minsk, Belarus.
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Khrustaleva
authors.affiliation: School of Basic Sciences, Indian Institute of Technology Mandi Mandi, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Sharma
authors.affiliation: School of Basic Sciences, Indian Institute of Technology Mandi Mandi, India.
authors.forename: Rajanish
authors.initials: R
authors.lastname: Giri
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D005075:Biological Evolution; D019295:Computational Biology; D006801:Humans; D009154:Mutation; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012641:Selection, Genetic; D014779:Virus Replication; D000071244:Zika Virus / Q000235:genetics* / Q000502:physiology*
chemical_list: D012367:RNA, Viral; D000243:Adenosine Deaminase
keywords: ADAR-editing; Zika virus; mutational pressure; pauses in replication; ribosome stalling