Abstract
Jaagsiekte sheep retrovirus (JSRV) and ovine nasal adenocarcinoma virus (ONAV) replicate in the airway and cause epithelial cell tumors through the activity of their envelope (Env) proteins. Identification of the receptor(s) that mediate cell entry by these viruses is crucial to understanding the oncogenic activity of Env and for the development of gene therapy vectors based on these viruses that are capable of targeting airway cells. To identify the viral receptor(s) and to further study the biology of JSRV and ONAV, we developed retroviral vectors containing Moloney murine leukemia virus components and the Env proteins of JSRV or ONAV. We used a new technique involving positional cloning by phenotypic mapping in radiation hybrid cells to identify and clone the human receptor for JSRV, Hyal2, which also serves as the receptor for ONAV. Hyal2 is a glycosylphosphatidylinositol-anchored cell-surface protein that has low hyaluronidase activity and is a member of a large family that includes sperm hyaluronidase (Spam) and serum hyaluronidase (Hyal1). Hyal2 is located in a region of human chromosome 3p21.3 that is often deleted in lung cancer, suggesting that it may be a tumor suppressor. However, its role in JSRV or ONAV tumorigenesis, if any, is still unclear. JSRV vectors are capable of transducing various human cells, and are being further evaluated for gene therapy purposes.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Albritton LM, Tseng L, Scadden D, Cunningham JM (1989) A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection. Cell 57:659–666
Battini JL, Rasko JEJ, Miller AD (1999) A human cell-surface receptor for xenotropic and polytropic murine leukemia viruses: Possible role in G protein-coupled signal transduction. Proc Natl Acad Sci USA 96:1385–1390
Coil DA, Strickler JH, Rai SK, Miller AD (2001) Jaagsiekte sheep retrovirus Env protein stabilizes retrovirus vectors against inactivation by lung surfactant, centrifugation, and freeze-thaw cycling. J Virol 75:8864–8867
Csoka AB, Scherer SW, Stern R (1999) Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. Genomics 60:356–361
Dalgleish AG, Beverly PCL, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763–767
Dirks C, Duh FM, Rai SK, Lerman MI, Miller AD (2002) Mechanism of cell entry and transformation by enzootic nasal tumor virus. J Virol 76:2141–2149
Dirks C, Duh F-M, Rai SK, Lerman MI, and Miller AD (2002) Mechanism of Cell Entry and Transformation by Enzootic Nasal Tumor Virus. J Virol 76:2141-2149
Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, Gluckman JC, Montagnier L (1984) T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312:767–768
Lepperdinger G, Strobl B, Kreil G (1998) HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. J Biol Chem 273:22466–22470
Lerman MI, Minna JD, for The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium (2000) The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: Identification and evaluation of the resident candidate tumor suppressor genes. Cancer Res 60:6116–6133
Maeda N, Palmarini M, Murgia C, Fan H (2001) Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA. Proc Natl Acad Sci USA 98:4449–4454
Miller AD, Chen F (1996) Retrovirus packaging cells based on 10A1 murine leukemia virus for production of vectors that use multiple receptors for cell entry. J Virol 70:5564–5571
Miller AD, Garcia JV, Von Suhr N, Lynch CM, Wilson C, Eiden MV (1991) Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus. J Virol 65:2220–2224
Miller DG, Edwards RH, Miller AD (1994) Cloning of the cellular receptor for amphotropic murine retroviruses reveals homology to that for gibbon ape leukemia virus. Proc Natl Acad Sci USA 91:78–82
O’Hara B, Johann SV, Klinger HP, Blair DG, Rubinson H, Dunn KJ, Sass P, Vitek SM, Robins T (1990) Characterization of a human gene conferring sensitivity to infection by gibbon ape leukemia virus. Cell Growth & Differentiation 1:119–127
Overbaugh J, Miller AD, Eiden MV (2001) Receptors and entry cofactors for retroviruses include single and multiple transmembrane-spanning proteins as well as newly described glycosylphosphatidylinositol-anchored and secreted proteins. Microbiol Molec Biol Rev 65:371–389
Palmarini M, Holland MJ, Cousens C, Dalziel RG, Sharp JM (1996) Jaagsiekte retrovirus establishes a disseminated infection of the lymphoid tissues of sheep affected by pulmonary adenomatosis. J Gen Virol 77:2991–2998
Palmarini M, Maeda N, Murgia C, De-Fraja C, Hofacre A, Fan H (2001) A phosphatidylinositol 3-kinase docking site in the cytoplasmic tail of the jaagsiekte sheep retrovirus transmembrane protein is essential for envelope-induced transformation of NIH 3T3 cells. J Virol 75:11002–11009
Palmarini M,Sharp JM,De las Heras M,Fan H (1999a) Jaagsiekte sheep retrovirus is necessary and sufficient to induce a contagious lung cancer in sheep. J Virol 73:6964-6972
Palmarini M, Sharp JM, Lee C, Fan H (1999b) In vitro infection of ovine cell lines by Jaagsiekte sheep retrovirus. J Virol 73:10070–10078
Rai SK, Demartini JC, Miller AD (2000) Retrovirus vectors bearing the jaagsiekte sheep retrovirus Env transduce human cells by using a new receptor localized to chromosome 3p21.3. J Virol 74:4698–4704
Rai SK, Duh FM, Vigdorovich V, Danilkovitch-Miagkova A, Lerman MI, Miller AD (2001) Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Sci USA 98: 4443–4448
Rasko JEJ, Battini JL, Kruglyak L, Cox DR, Miller AD (2000) Precise gene localization by phenotypic assay of radiation hybrid cells. Proc Natl Acad Sci USA 97: 7388–7392
Sekido Y, Ahmadian M, Wistuba II, Latif F, Bader S, Wei MH, Duh FM, Gazdar AF, Lerman MI, Minna JD (1998) Cloning of a breast cancer homozygous deletion junction narrows the region of search for a 3p21.3 tumor suppressor gene. Oncogene 16:3151–3157
Strobl B, Wechselberger C, Beier DR, Lepperdinger G (1998) Structural organization and chromosomal localization of Hyal2, a gene encoding a lysosomal hyaluronidase. Genomics 53:214–219
Wei MH, Latif F, Bader S, Kashuba V, Chen JY, Duh FM, Sekido Y, Lee CC, Geil L, Kuzmin I, Zabarovsky E, Klein G, Zbar B, Minna JD, Lerman MI (1996) Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG. Cancer Res 56:1487–1492
Wistuba II, Montellano FD, Milchgrub S, Virmani AK, Behrens C, Chen H, Ahmadian M, Nowak JA, Muller C, Minna JD, Gazdar AF (1997) Deletions of chromosome 3p are frequent and early events in the pathogenesis of uterine cervical cancer. Cancer Res 57:3154–3158
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Miller, A.D. (2003). Identification of Hyal2 as the Cell-Surface Receptor for Jaagsiekte Sheep Retrovirus and Ovine Nasal Adenocarcinoma Virus. In: Fan, H. (eds) Jaagsiekte Sheep Retrovirus and Lung Cancer. Current Topics in Microbiology and Immunology, vol 275. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55638-8_7
Download citation
DOI: https://doi.org/10.1007/978-3-642-55638-8_7
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-62897-9
Online ISBN: 978-3-642-55638-8
eBook Packages: Springer Book Archive