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

Area of Science:

• Virology
• Molecular Evolution
• Genetics

Background:

• Zika virus (ZIKV), a mosquito-borne flavivirus, is associated with severe human health issues like microcephaly.
• Host-mediated RNA editing, specifically adenosine deaminases acting on RNA (ADAR), is a cellular process with implications for RNA virus evolution.
• The precise role of ADAR editing in the molecular evolution of ZIKV and other RNA viruses remains incompletely understood.

Purpose of the Study:

• To investigate the role of host-mediated RNA editing of adenosines (ADAR) in the molecular evolution of Zika virus (ZIKV).
• To determine if ADAR editing acts as a mutation and evolutionary force in both positive- and negative-strand RNA viruses.

Main Methods:

• Analysis of complete coding sequences of the ZIKV polyprotein.
• Examination of potential ADAR substitutions at ADAR-resistant GA dinucleotides on both positive and negative viral RNA strands.
• Phylogenetic analysis to assess spatial and temporal clustering of editing events.
• Investigation of the relationship between ADAR mutagenesis and viral codon usage.

Main Results:

• Potential ADAR substitutions were underrepresented at ADAR-resistant GA dinucleotides in ZIKV.
• ADAR-induced changes showed spatial and temporal clustering across three viral phylogenetic branches.
• ADAR mutagenesis was linked to ZIKV codon usage.
• Resistant GA dinucleotides were enriched on the positive strand, suggesting stronger purifying selection compared to the negative strand.
• ADAR editing was also found to influence the evolution of rhabdovirus sigma.

Conclusions:

• Host ADAR editing is a significant mutation and evolutionary force impacting both positive- and negative-strand RNA viruses, including ZIKV.
• The findings highlight the interplay between host cellular machinery and viral evolution.
• ADAR editing contributes to the molecular diversification and adaptation of RNA viruses.