Cousens, C. | Search bioRxiv

bioRxiv2025

Genome sequence and annotation of ovine herpesvirus-1

Ovine herpesvirus 1 (OvHV-1) was first identified over 50 years ago in sheep with ovine pulmonary adenocarcinoma (OPA). An aetiological role in OPA was later ruled out and OvHV-1 was found to be a common infection in sheep in several countries. Here, we report the sequence and annotation of the complete OvHV-1 genome. The virus has a similar genomic architecture to members of the Macavirus genus of the subfamily Gammaherpesvirinae and is most closely related to bovine gammaherpesvirus 6 (BoGHV6). The OvHV-1 genome comprises a 144,637 base pair unique region predicted to encode at least 74 proteins bounded by multiple copies of a 699 base pair GC-rich repetitive terminal repeat. Predicted genes include 61 ORFs conserved among all gammaherpesviruses, and 12 genes present only in macavirus genomes, including a homologue of ovine interleukin-10, previously reported only in ovine gammaherpesvirus-2, and an ornithine decarboxylase, previously described only in BoGHV6. A further gene appears unique to OvHV-1 among macaviruses, encoding a viral-FLIP (FLICE-like inhibitory protein), similar to those found in some other gammaherpesviruses. Notably, several macavirus genes previously predicted in BoGHV6 are defective in OvHV-1. The availability of the genome sequence of OvHV-1 will facilitate studies on its relationship to other macaviruses and its role, if any, in disease.

microbiology↗

bioRxiv2021

Jaagsiekte sheep retrovirus infection induces changes in microRNA expression in the ovine lung

Ovine pulmonary adenocarcinoma (OPA) is an infectious neoplastic lung disease of sheep caused by jaagsiekte sheep retrovirus. OPA is an important veterinary problem and is also a valuable large animal model for human lung adenocarcinoma. JSRV infects type 2 alveolar epithelial cells in the lung and induces the growth of tumors, but little is known about the molecular events that lead to the activation of oncogenic pathways in infected cells. MicroRNAs (miRNAs) are small RNA molecules of approximately 22 nucleotides with important roles in regulating gene expression in eukaryotes and with well-established roles in cancer. Here we used small-RNA sequencing to investigate the changes in miRNA expression that occur in JSRV-infected ovine lung. After filtering out low abundance miRNAs, we identified expression of 405 miRNAs, 32 of which were differentially expressed in JSRV-infected lung compared to mock-inoculated control lung. Highly upregulated miRNAs included miR-182, miR-183, miR-96 and miR-135b, which have also been associated with oncogenic changes in human lung cancer. Network analysis of genes potentially targeted by the deregulated miRNAs identified their involvement in pathways known to be dysregulated in OPA. We found no evidence to support the existence of miRNAs encoded by JSRV. This study provides the first information on miRNA expression in OPA and identifies a number of targets for future studies into the role of these molecules in the pathogenesis of this unique veterinary model for human lung adenocarcinoma. IMPORTANCEOvine pulmonary adenocarcinoma is a neoplastic lung disease of sheep caused by jaagsiekte sheep retrovirus (JSRV). OPA is a significant welfare and economic concern for sheep producers and is a valuable large animal model for human lung adenocarcinoma. MicroRNAs are small RNA molecules of approximately 22 nucleotides with important functions in regulating gene expression in eukaryotes and with well-established roles in cancer. In this study, we examined the changes in microRNA expression that occur in the lung in response to JSRV infection. We identified differential expression of a number of host-encoded microRNAs in infected tissue, including microRNAs with roles in human cancer. We found no evidence that JSRV encodes a microRNA. This study provides new insights on the cellular response to JSRV infection in the ovine lung, which will inform future studies into the pathogenesis of OPA in sheep and its use as a model for human lung adenocarcinoma.

microbiology↗