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Macropodid herpesvirus 1 encodes genes for both thymidylate synthase and ICP34.5
Sandeep Guliani1, Ian Polkinghorne, Greg A Smith
1Queensland Agricultural Biotechnology Centre, Gehrmann Laboratories, St. Lucia, Brisbane, Australia. sguliani@hotmail.com
Abstract:
Macropodid herpesvirus 1 (MaHV-1) is an unclassified alphaherpesvirus linked with the fatal infections of kangaroos and other marsupials. During the characterisation of the internal repeat region of MaHV-1, an open reading frame (ORF) encoding for thymidylate synthase (TS) gene was identified and completely sequenced. Southern blot analysis confirmed the presence of two copies of the TS gene in the MaHV-1 genome as expected. Computer analysis of the TS ORF showed it was 948 nucleotides in length. A putative polyadenylation signal was identified 17-22 bp inside the ORF implying a minimal or absent 3' untranslated region. The predicted polypeptide was 316 amino acid residues in length and contained the highly conserved motifs for folate binding and F-dUMP binding, typical of all TS enzymes. Interestingly, MaHV-1 TS polypeptide had highest similarity to the human TS polypeptide (81%) compared to the TS polypeptides of other herpesviruses (72-75%). Immediately upstream of the TS gene, a second ORF of 510 bp, encoding a polypeptide with 170 amino acid residues, was identified. The carboxyl domain of this MaHV-1 polypeptide shared 68% similarity to a 59 amino acid motif of human herpesvirus 1 ICP34.5, identifying it as the MaHV-1 ICP34.5 homologue. This is the first report of a herpesvirus that encodes for both TS and ICP34.5.
Insights
Macropodid herpesvirus 1 encodes thymidylate synthase (TS) and ICP34.5, crucial genes not previously found together in any herpesvirus. This discovery offers new insights into marsupial herpesvirus genetics and pathogenesis.
Area of Science:
- Virology
- Genomics
- Comparative Biology
Background:
- Macropodid herpesvirus 1 (MaHV-1) is an unclassified alphaherpesvirus associated with severe, fatal infections in marsupials.
- Understanding MaHV-1's genetic makeup is crucial for marsupial health and conservation efforts.
Purpose of the Study:
- To characterize novel genes within the MaHV-1 genome.
- To identify and analyze open reading frames (ORFs) encoding thymidylate synthase (TS) and its associated proteins.
Main Methods:
- DNA sequencing of the MaHV-1 internal repeat region.
- Bioinformatic analysis of identified ORFs.
- Southern blot analysis to confirm gene copy number.
Main Results:
- Identification and sequencing of a MaHV-1 thymidylate synthase (TS) gene with two copies in the genome.
- The MaHV-1 TS polypeptide shares 81% similarity with human TS and possesses conserved functional motifs.
- Discovery of a MaHV-1 ICP34.5 homologue gene upstream of the TS gene, sharing 68% similarity with human herpesvirus 1 ICP34.5.
Conclusions:
- This study reports, for the first time, a herpesvirus encoding both thymidylate synthase and ICP34.5.
- The findings provide significant insights into the unique genetic adaptations of MaHV-1 and its potential pathogenic mechanisms in marsupials.