PMID- 31739606 OWN - NLM STAT- MEDLINE DCOM- 20200916 LR - 20200916 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 11 IP - 11 DP - 2019 Nov 14 TI - The U3 and Env Proteins of Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Both Contribute to Tissue Tropism. LID - 10.3390/v11111061 [doi] LID - 1061 AB - Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are small-ruminant betaretroviruses that share high nucleotide and amino acid identity, utilize the same cellular receptor, hyaluronoglucosaminidase 2 (Hyal2) for entry, and transform tissues with their envelope (Env) glycoprotein; yet, they target discrete regions of the respiratory tract-the lung and nose, respectively. This distinct tissue selectivity makes them ideal tools with which to study the pathogenesis of betaretroviruses. To uncover the genetic determinants of tropism, we constructed JSRV-ENTV chimeric viruses and produced lentivectors pseudotyped with the Env proteins from JSRV (Jenv) and ENTV (Eenv). Through the transduction and infection of lung and nasal turbinate tissue slices, we observed that Hyal2 expression levels strongly influence ENTV entry, but that the long terminal repeat (LTR) promoters of these viruses are likely responsible for tissue-specificity. Furthermore, we show evidence of ENTV Env expression in chondrocytes within ENTV-infected nasal turbinate tissue, where Hyal2 is highly expressed. Our work suggests that the unique tissue tropism of JSRV and ENTV stems from the combined effort of the envelope glycoprotein-receptor interactions and the LTR and provides new insight into the pathogenesis of ENTV. FAU - Rosales Gerpe, Maria C AU - Rosales Gerpe MC AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - van Lieshout, Laura P AU - van Lieshout LP AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - Domm, Jakob M AU - Domm JM AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - Ingrao, Joelle C AU - Ingrao JC AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - Datu, Jodre AU - Datu J AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - Walsh, Scott R AU - Walsh SR AD - McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Hamilton ON L8S 4L8, Ontario, Canada. FAU - Yu, Darrick L AU - Yu DL AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - Jong, Jondavid de AU - Jong J AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - Krell, Peter J AU - Krell PJ AD - Department of Cellular and Molecular Biology, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. FAU - Wootton, Sarah K AU - Wootton SK AD - Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph ON N1G 2W1, Ontario, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191114 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Gene Products, env) SB - IM MH - Animals MH - Cell Line MH - Gene Order MH - Gene Products, env/*genetics MH - Genome, Viral MH - Host Specificity MH - Host-Pathogen Interactions MH - Humans MH - Jaagsiekte sheep retrovirus/*physiology MH - Oncogenic Viruses/*physiology MH - Pulmonary Adenomatosis, Ovine/*virology MH - Reassortant Viruses/genetics MH - Sheep MH - *Terminal Repeat Sequences MH - Tumor Virus Infections/*virology MH - *Viral Tropism PMC - PMC6893448 OTO - NOTNLM OT - chimeric virus OT - envelope glycoproteins OT - long terminal repeat (LTR), sheep betaretroviruses OT - pathogenesis OT - pseudotyping OT - tropism COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2019/11/20 06:00 MHDA- 2020/09/17 06:00 PMCR- 2019/11/01 CRDT- 2019/11/20 06:00 PHST- 2019/10/25 00:00 [received] PHST- 2019/11/12 00:00 [revised] PHST- 2019/11/12 00:00 [accepted] PHST- 2019/11/20 06:00 [entrez] PHST- 2019/11/20 06:00 [pubmed] PHST- 2020/09/17 06:00 [medline] PHST- 2019/11/01 00:00 [pmc-release] AID - v11111061 [pii] AID - viruses-11-01061 [pii] AID - 10.3390/v11111061 [doi] PST - epublish SO - Viruses. 2019 Nov 14;11(11):1061. doi: 10.3390/v11111061.