Open AccessGenome-wide transposon mutagenesis of paramyxoviruses reveals constraints on genomic plasticity
Author(s) -
Satoshi Ikegame,
Shan M. Beaty,
Christian S. Stevens,
Taylor Sohiu Won,
Arnold Park,
David Sachs,
Patrick Hong,
Benhur Lee,
Patricia A. Thibault
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008877
Subject(s) - transposable element , sleeping beauty transposon system , biology , genome , transposon mutagenesis , genetics , mutagenesis , computational biology , mutation , gene
The antigenic and genomic stability of paramyxoviruses remains a mystery. Here, we evaluate the genetic plasticity of Sendai virus (SeV) and mumps virus (MuV), sialic acid-using paramyxoviruses that infect mammals from two Paramyxoviridae subfamilies ( Orthoparamyxovirinae and Rubulavirinae ). We performed saturating whole-genome transposon insertional mutagenesis, and identified important commonalities: disordered regions in the N and P genes near the 3' genomic end were more tolerant to insertional disruptions; but the envelope glycoproteins were not, highlighting structural constraints that contribute to the restricted antigenic drift in paramyxoviruses. Nonetheless, when we applied our strategy to a fusion-defective Newcastle disease virus ( Avulavirinae subfamily), we could select for F-revertants and other insertants in the 5' end of the genome. Our genome-wide interrogation of representative paramyxovirus genomes from all three Paramyxoviridae subfamilies provides a family-wide context in which to explore specific variations within and among paramyxovirus genera and species.