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Viruses 2018, 10(9), 464; https://doi.org/10.3390/v10090464

Transcriptome Analysis and In Situ Hybridization for FcaGHV1 in Feline Lymphoma

1
Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, NSW 2006, Australia
2
School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia
3
Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW 2006, Australia
4
School of Veterinary Medicine, Department of Pathology, Microbiology, and Immunology, University of California at Davis, Davis, CA 95616, USA
5
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA
6
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada
*
Author to whom correspondence should be addressed.
Received: 19 August 2018 / Revised: 28 August 2018 / Accepted: 28 August 2018 / Published: 30 August 2018
(This article belongs to the Special Issue Nonprimate Lentivirus)
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Abstract

Lymphoma is one of the most common malignancies in domestic cats. The lymphomagenic potential of Felis catus gammaherpesvirus 1 (FcaGHV1), a common infection in domestic cats, is unknown. In other species, including humans, cellular transformation by gammaherpesviruses is typically mediated by viral genes expressed during latency. We analysed tumour RNA, from diffuse large B-cell lymphomas (DLBCL) appearing in cats coinfected with FcaGHV1 and feline immunodeficiency virus (FIV) (n = 10), by high throughput transcriptome sequencing and reverse transcription PCR. A limited repertoire of FcaGHV transcripts was identified in five tumors, including homologs of oncogenic latency-associated transcripts, latency-associated nuclear antigen (LANA, ORF73) and vFLIP (F7), lytic genes (ORF50, ORF6, ORF59, F10), and an ORF unique to FcaGHV1, F20. In situ hybridization of FIV-associated DLBCLs (n = 9), post-transplant lymphomas (n = 6) and high-grade B and T-cell intestinal lymphomas (n = 8) identified a single case in which FcaGHV1 nucleic acid was detectable. These results demonstrate that FcaGHV1 transcripts can be detected in some FIV-associated lymphomas, but at low copy number, precluding assessment of a potential role for FcaGHV1 in lymphomagenesis. Future investigation of the FcaGHV1 transcriptome in clinical samples might employ viral enrichment and greater sequencing depth to enhance the retrieval of viral reads. Our results suggest prioritization of a subset of intestinal T-cell tumors, large granular lymphocyte lymphoma, for study. View Full-Text
Keywords: gammaherpesvirus; immunodeficiency; virus; domestic cat; felid; lymphomagenesis; oncogenic; transcriptome; lymphoma; cancer; B-cell; T-cell gammaherpesvirus; immunodeficiency; virus; domestic cat; felid; lymphomagenesis; oncogenic; transcriptome; lymphoma; cancer; B-cell; T-cell
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Aghazadeh, M.; Shi, M.; Pesavento, P.A.; Durham, A.C.; Polley, T.; Donahoe, S.L.; Troyer, R.M.; Barrs, V.R.; Holmes, E.C.; Beatty, J.A. Transcriptome Analysis and In Situ Hybridization for FcaGHV1 in Feline Lymphoma. Viruses 2018, 10, 464.

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