Open AccessStructural analysis of viral ExoN domains reveals polyphyletic hijacking events
Author(s) -
Adrián Cruz-González,
Israel MuñozVelasco,
Wolfgang Cottom-Salas,
Arturo Becerra,
José Alberto Campillo-Balderas,
Ricardo Hernández-Morales,
Alberto Vázquez-Salazar,
Rodrigo Jácome,
Antonio Lazcano
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0246981
Subject(s) - biology , exon , zinc finger , proofreading , rna , genetics , exon shuffling , computational biology , polymerase , gene , tandem exon duplication , transcription factor
Nidoviruses and arenaviruses are the only known RNA viruses encoding a 3’-5’ exonuclease domain (ExoN). The proofreading activity of the ExoN domain has played a key role in the growth of nidoviral genomes, while in arenaviruses this domain partakes in the suppression of the host innate immune signaling. Sequence and structural homology analyses suggest that these proteins have been hijacked from cellular hosts many times. Analysis of the available nidoviral ExoN sequences reveals a high conservation level comparable to that of the viral RNA-dependent RNA polymerases (RdRp), which are the most conserved viral proteins. Two highly preserved zinc fingers are present in all nidoviral exonucleases, while in the arenaviral protein only one zinc finger can be identified. This is in sharp contrast with the reported lack of zinc fingers in cellular ExoNs, and opens the possibility of therapeutic strategies in the struggle against COVID-19.