A novel spliced gene in alcelaphine herpesvirus 1 encodes a glycoprotein which is secreted in vitro

J Gen Virol. 2013 Nov;94(Pt 11):2515-2523. doi: 10.1099/vir.0.055673-0. Epub 2013 Aug 16.

Abstract

Herpesviruses often contain cryptic, spliced genes that are not obvious from the initial in silico annotation. Alcelaphine herpesvirus 1 (AlHV-1) contains 72 annotated ORFs but there are also a number of gaps between these that may have protein-coding potential. Comparative analysis of coding potential between AlHV-1 and the related ovine herpesvirus 2 (OvHV-2) revealed a putative novel spliced gene that we have termed A9.5. Analysis of cDNA clones from AlHV-1-infected cells revealed three overlapping clones corresponding to A9.5 and the coding sequence was confirmed by reverse transcription PCR of RNA from AlHV-1-infected cattle tissues. The A9.5 gene was predicted to encode a secreted glycoprotein with molecular mass 19 kDa. Empirical analysis showed that a recombinant haemagglutinin-tagged A9.5 fusion protein was secreted from transfected cells and had a molecular mass of 45 kDa, which was reduced to 20 kDa by endoglycosidase F treatment, confirming that A9.5 was a secreted glycoprotein. In situ RNA hybridization showed that A9.5 was expressed in cells associated with malignant catarrhal fever (MCF) lesions in infected cattle. Detailed analysis of the available OvHV-2 sequences revealed an homologous gene (Ov9.5) with conserved splicing signals and predicted amino acid sequence features in both sequenced isolates of this related virus. We have therefore identified a novel spliced gene in two related macaviruses that is expressed in MCF lesions. Future work will determine its importance for the pathogenesis of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cattle Diseases / virology*
  • DNA, Recombinant / genetics*
  • Gammaherpesvirinae / classification*
  • Gammaherpesvirinae / genetics*
  • Gammaherpesvirinae / metabolism
  • Glycoproteins / chemistry
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / virology
  • Kidney / virology
  • Malignant Catarrh / virology*
  • Molecular Sequence Data
  • Sequence Analysis, DNA

Substances

  • DNA, Recombinant
  • Glycoproteins

Associated data

  • GENBANK/FN553440
  • GENBANK/HE855448
  • GENBANK/HE855449
  • GENBANK/HE855450
  • GENBANK/HE855451
  • GENBANK/HE855452