Summary auto-generated
Murine gammaherpesvirus 68 (MHV-68) is a rodent pathogen used as a model for studying gammaherpesvirus infection. Researchers sequenced 6,162 base pairs of the MHV-68 genome and discovered eight novel tRNA-like sequences interspersed with three open reading frames. These tRNA-like sequences contain characteristic tRNA features including cloverleaf secondary structures and RNA polymerase III promoter elements (box A and B motifs). During lytic infection, these sequences are transcribed and processed into mature tRNAs with post-transcriptionally added 3' CCA termini, demonstrating cellular recognition as functional tRNAs. However, acidic Northern analysis revealed that four tested viral tRNAs are not aminoacylated by cellular aminoacyl-tRNA synthetases, indicating they do not function in conventional protein translation. Notably, in situ hybridization showed that these tRNA-like sequences are abundantly expressed in splenic germinal centers of latently infected mice, suggesting they serve as markers of latent infection. One ORF (ORF1) shows homology to poxvirus serpins. This represents the first report of tRNA-like sequences encoded by a eukaryotic virus, with unclear biological function for the non-functional tRNAs.
Key findings
- MHV-68 encodes eight novel tRNA-like sequences that are transcribed and processed into mature tRNAs with functional 3' CCA termini during lytic infection
- The viral tRNA-like sequences are not aminoacylated by cellular aminoacyl-tRNA synthetases and do not function in conventional translation
- Viral tRNA-like sequences are abundantly expressed in splenic germinal centers of latently infected mice, making them markers of latent infection
- One open reading frame (ORF1) shows sequence homology to poxvirus serpin proteins
- This is the first report of tRNA-like sequences encoded by any eukaryotic virus
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Abstract
Murine gammaherpesvirus 68 (MHV-68) is a virus of wild rodents and is a convenient small animal model for studies of gammaherpesvirus pathogenesis. We have sequenced 6162 bp at the left end of the MHV-68 genome and identified two unique open reading frames (ORFs) (ORF2 and ORF3) and an ORF (ORF1) which displays similarity to poxvirus members of the serpin family. Interspersed with the ORFs is a family of eight novel tRNA-like sequences sharing tRNA-like predicted secondary structures and RNA polymerase III promoter elements. These sequences are expressed to high levels during lytic infection and are processed into mature tRNAs with post-transcriptionally added 3' CCA termini, indicating their recognition as tRNAs by cellular machinery. Acidic Northern analysis of four tRNAs tested has demonstrated that they are not aminoacylated by aminoacyl-tRNA synthetases present in the infected cell. Thus, it is currently unclear what biological function these uncharged viral tRNA-like sequences may fulfil. In situ hybridization analysis has shown that in addition to being expressed within productively infected tissues during acute stages of infection, the tRNA-like sequences are abundantly expressed within splenic germinal centres of latently infected mice. Therefore, the MHV-68 viral tRNAs represent a marker for latent infection and constitute the first report of tRNA-like sequences encoded by a virus of eukaryotes.