RT Journal Article
SR Electronic
T1 Upstream translation initiation expands the coding capacity of segmented negative-strand RNA viruses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 795815
DO 10.1101/795815
A1 Elizabeth Sloan
A1 Marta Alenquer
A1 Liliane Chung
A1 Sara Clohisey
A1 Adam M. Dinan
A1 Robert Gifford
A1 Quan Gu
A1 Nerea Irigoyen
A1 Joshua D. Jones
A1 Ingeborg van Knippenberg
A1 Veronica Rezelj
A1 Bo Wang
A1 Helen M. Wise
A1 Maria Joao Amorim
A1 J Kenneth Baillie
A1 Ian Brierley
A1 Paul Digard
A1 Andrew E. Firth
A1 Megan K. MacLeod
A1 Edward Hutchinson
YR 2019
UL http://biorxiv.org/content/early/2019/10/08/795815.abstract
AB Segmented negative-strand RNA viruses (sNSVs) include the influenza viruses, the bunyaviruses, and other major pathogens of humans, other animals and plants. The genomes of these viruses are extremely short. In response to this severe genetic constraint, sNSVs use a variety of strategies to maximise their coding potential. Because the eukaryotic hosts parasitized by sNSVs can regulate gene expression through low levels of translation initiation upstream of their canonical open reading frames (ORFs), we asked whether sNSVs could use upstream translation initiation to expand their own genetic repertoires. Consistent with this hypothesis, we showed that influenza A viruses (IAVs) and bunyaviruses were capable of upstream translation initiation. Using a combination of reporter assays and viral infections, we found that upstream translation in IAVs can initiate in two unusual ways: through non-AUG initiation in virally encoded ‘untranslated’ regions, and through the appropriation of an AUG-containing leader sequence from host mRNAs through viral cap-snatching, a process we termed ‘start-snatching.’ Finally, while upstream translation of cellular genes is mainly regulatory, for sNSVs it also has the potential to create novel viral gene products. If in frame with a viral ORF, this creates N-extensions of canonical viral proteins. If not, it allows the expression of cryptic overlapping ORFs, which we found were highly conserved in IAV and widely distributed in peribunyaviruses. Thus, by exploiting their host’s capacity for upstream translation initiation, sNSVs can expand still further the coding potential of their extremely compact RNA genomes.