title: Evidence against a role for jaagsiekte sheep retrovirus in human lung cancer.
abstract: Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats that can be transmitted by aerosols produced by infected animals. Virus entry into cells is initiated by binding of the viral envelope (Env) protein to a specific cell-surface receptor, Hyal2. Unlike almost all other retroviruses, the JSRV Env protein is also a potent oncoprotein and is responsible for lung cancer in animals. Of concern, Hyal2 is a functional receptor for JSRV in humans.
  
  
  
  We show here that JSRV is fully capable of infecting human cells, as measured by its reverse transcription and persistence in the DNA of cultured human cells. Several studies have indicated a role for JSRV in human lung cancer while other studies dispute these results. To further investigate the role of JSRV in human lung cancer, we used highly-specific mouse monoclonal antibodies and a rabbit polyclonal antiserum against JSRV Env to test for JSRV expression in human lung cancer. JSRV Env expression was undetectable in lung cancers from 128 human subjects, including 73 cases of bronchioalveolar carcinoma (BAC; currently reclassified as lung invasive adenocarcinoma with a predominant lepidic component), a lung cancer with histology similar to that found in JSRV-infected sheep. The BAC samples included 8 JSRV DNA-positive samples from subjects residing in Sardinia, Italy, where sheep farming is prevalent and JSRV is present. We also tested for neutralizing antibodies in sera from 138 Peruvians living in an area where sheep farming is prevalent and JSRV is present, 24 of whom were directly exposed to sheep, and found none.
  
  
  
  We conclude that while JSRV can infect human cells, JSRV plays little if any role in human lung cancer.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA. dmiller@fredhutch.org.|Department of Pathology, University of Washington, Seattle, WA, USA. dmiller@fredhutch.org.|, 17915 Edmundson Rd, Sisters, OR, 97759, USA. dmiller@fredhutch.org.
authors.forename: A Dusty
authors.identifier: 0000-0002-3736-3660
authors.initials: AD
authors.lastname: Miller
authors.affiliation: Department of Animal Pathology, Zaragoza University, Zaragoza, Spain.
authors.forename: Marcelo
authors.identifier: 0000-0003-3792-287X
authors.initials: M
authors.lastname: De Las Heras
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.|Department of Molecular Microbiology and Immunology, Bond Life Sciences Canter, University of Missouri, Columbia, MO, USA.
authors.forename: Jingyou
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Canter, University of Missouri, Columbia, MO, USA.
authors.forename: Fushun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.|Department of Molecular Microbiology and Immunology, Bond Life Sciences Canter, University of Missouri, Columbia, MO, USA.
authors.forename: Shan-Lu
authors.identifier: 0000-0003-1620-3817
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Vaughan
authors.affiliation: Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Thomas L
authors.identifier: 0000-0003-1537-0242
authors.initials: TL
authors.lastname: Vaughan
authors.affiliation: Veterinary Faculty, National University of San Marcos, Lima, Peru.
authors.forename: Raul
authors.initials: R
authors.lastname: Rosadio
authors.affiliation: Department of Veterinary Medicine, Sassari University, Sassari, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rocca
authors.affiliation: Unit of Cancer Genetics, Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy.
authors.forename: Giuseppe
authors.identifier: 0000-0002-4350-2276
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Junya
authors.initials: J
authors.lastname: Fujimoto
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000821:virology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000822:Animal Husbandry; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D022141:Jaagsiekte sheep retrovirus / Q000302:isolation & purification* / Q000472:pathogenicity*; D008175:Lung Neoplasms / Q000473:pathology* / Q000821:virology*; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D016273:Occupational Exposure; D014759:Viral Envelope Proteins / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins
keywords: Human lung cancer; Jaagsiekte sheep retrovirus; Ovine pulmonary adenocarcinoma