Selection of a 33-nt intraleader open reading frame attenuates translation of downstream open reading frames in bovine coronavirus mRNAs, potentially maintaining persistent infection.
Selection of an intraleader open reading frame attenuates mRNA translation, providing a potential mechanism for coronaviruses to maintain persistent infection.
Short open reading frames within the 5' leader of some eukaryotic mRNAs are known to regulate the rate of translation initiation on the downstream open reading frame. By employing the polymerase chain reaction, we learned that the 5'-terminal 5 nt on the common leader sequence of bovine coronavirus subgenomic mRNAs were heterogeneous and hypervariable throughout early infection in cell culture and that as a persistent infection became established, termini giving rise to a common 33-nt intraleader open reading frame were selected. Since the common leader is derived from the genomic 5' end during transcription, a common focus of origin for the heterogeneity is expected. The intraleader open reading frame was shown by in vitro translation studies to attenuate translation of downstream open reading frames in a cloned bovine coronavirus mRNA molecule. Selection of an intraleader open reading frame resulting in a general attenuation of mRNA translation and a consequent attenuation of virus replication may, therefore, be a mechanism by which coronaviruses and possibly other RNA viruses with a similar transcriptional strategy maintain a persistent infection.
Hofmann‐Apitius et al. (Wed,) conducted a other in Bovine coronavirus infection. Intraleader open reading frame was evaluated on Translation of downstream open reading frames. Selection of a 33-nt intraleader open reading frame attenuates translation of downstream open reading frames in bovine coronavirus mRNAs, potentially maintaining persistent infection.