Transformation of rodent fibroblasts by the Jaagsiekte sheep retrovirus envelope is receptor independent and does not require the surface domain

Yen Hung J. Chow, Alberto Alberti, Manuela Mura, Carla Pretto, Pablo Murcia, Lorraine Albritton, Massimo Palmarini

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). Expression of the JSRV envelope protein (Env) is sufficient to transform immortalized and primary fibroblasts, but the precise mechanisms of this process are not known. The cellular receptor for JSRV is hyaluronidase 2 (Hyal-2), the product of a putative tumor suppressor gene that in humans maps to a chromosomal region frequently deleted in the development of lung and breast cancers. Here we report studies to determine whether the Hyal-2-JSRV Env interaction plays a role in virus-induced transformation of rodent fibroblasts. Chimeric Env proteins between JSRV and the unrelated murine retroviruses Moloney murine leukemia virus (MMuLV) and mouse mammary tumor virus (MMTV) showed cell surface expression comparable to that of wild-type MMuLV Env and rescued infection of MMuLV particle pseudotypes. Interestingly, an MMuLV-JSRV chimera in which the putative receptor binding domain (RBD) and proline-rich region (PRR) of JSRV Env were replaced by the RBD and PRR of MMuLV induced transformation of 208F, a rodent fibroblast line. Cell lines derived from foci of MMuLV-JSRV chimeratransformed 208F cells grew in soft agar and showed Akt activation, a hallmark of JSRV-transformed rodent fibroblasts. Transformation assays performed using proteins with amino-terminal deletion mutations showed that the carboxy-terminal 141 amino acids of the transmembrane subunit (TM) were sufficient to induce cell transformation when targeted to the membrane with a myristoylation signal. Thus, the JSRV TM is necessary and sufficient to transform rodent fibroblasts. Taken together these results indicate that the interaction with Hyal-2 at least is not an essential determinant of JSRV-induced transformation of fibroblasts and that the viral TM functions essentially as an oncoprotein.

Original languageEnglish (US)
Pages (from-to)6341-6350
Number of pages10
JournalJournal of Virology
Volume77
Issue number11
DOIs
StatePublished - Jun 1 2003

Fingerprint

Jaagsiekte sheep retrovirus
fibroblasts
Rodentia
Murine leukemia virus
rodents
Fibroblasts
Moloney murine leukemia virus
receptors
hyaluronoglucosaminidase
Hyaluronoglucosaminidase
lung neoplasms
Proline
proline
Lung Neoplasms
Sheep
Retroviridae Proteins
Retroviridae
Mouse mammary tumor virus
ovine pulmonary adenomatosis
recombinant fusion proteins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Transformation of rodent fibroblasts by the Jaagsiekte sheep retrovirus envelope is receptor independent and does not require the surface domain. / Chow, Yen Hung J.; Alberti, Alberto; Mura, Manuela; Pretto, Carla; Murcia, Pablo; Albritton, Lorraine; Palmarini, Massimo.

In: Journal of Virology, Vol. 77, No. 11, 01.06.2003, p. 6341-6350.

Research output: Contribution to journalArticle

Chow, Yen Hung J. ; Alberti, Alberto ; Mura, Manuela ; Pretto, Carla ; Murcia, Pablo ; Albritton, Lorraine ; Palmarini, Massimo. / Transformation of rodent fibroblasts by the Jaagsiekte sheep retrovirus envelope is receptor independent and does not require the surface domain. In: Journal of Virology. 2003 ; Vol. 77, No. 11. pp. 6341-6350.
@article{5c1ecab98fad4d05949d3f3a83ff2e26,
title = "Transformation of rodent fibroblasts by the Jaagsiekte sheep retrovirus envelope is receptor independent and does not require the surface domain",
abstract = "Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). Expression of the JSRV envelope protein (Env) is sufficient to transform immortalized and primary fibroblasts, but the precise mechanisms of this process are not known. The cellular receptor for JSRV is hyaluronidase 2 (Hyal-2), the product of a putative tumor suppressor gene that in humans maps to a chromosomal region frequently deleted in the development of lung and breast cancers. Here we report studies to determine whether the Hyal-2-JSRV Env interaction plays a role in virus-induced transformation of rodent fibroblasts. Chimeric Env proteins between JSRV and the unrelated murine retroviruses Moloney murine leukemia virus (MMuLV) and mouse mammary tumor virus (MMTV) showed cell surface expression comparable to that of wild-type MMuLV Env and rescued infection of MMuLV particle pseudotypes. Interestingly, an MMuLV-JSRV chimera in which the putative receptor binding domain (RBD) and proline-rich region (PRR) of JSRV Env were replaced by the RBD and PRR of MMuLV induced transformation of 208F, a rodent fibroblast line. Cell lines derived from foci of MMuLV-JSRV chimeratransformed 208F cells grew in soft agar and showed Akt activation, a hallmark of JSRV-transformed rodent fibroblasts. Transformation assays performed using proteins with amino-terminal deletion mutations showed that the carboxy-terminal 141 amino acids of the transmembrane subunit (TM) were sufficient to induce cell transformation when targeted to the membrane with a myristoylation signal. Thus, the JSRV TM is necessary and sufficient to transform rodent fibroblasts. Taken together these results indicate that the interaction with Hyal-2 at least is not an essential determinant of JSRV-induced transformation of fibroblasts and that the viral TM functions essentially as an oncoprotein.",
author = "Chow, {Yen Hung J.} and Alberto Alberti and Manuela Mura and Carla Pretto and Pablo Murcia and Lorraine Albritton and Massimo Palmarini",
year = "2003",
month = "6",
day = "1",
doi = "10.1128/JVI.77.11.6341-6350.2003",
language = "English (US)",
volume = "77",
pages = "6341--6350",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Transformation of rodent fibroblasts by the Jaagsiekte sheep retrovirus envelope is receptor independent and does not require the surface domain

AU - Chow, Yen Hung J.

AU - Alberti, Alberto

AU - Mura, Manuela

AU - Pretto, Carla

AU - Murcia, Pablo

AU - Albritton, Lorraine

AU - Palmarini, Massimo

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). Expression of the JSRV envelope protein (Env) is sufficient to transform immortalized and primary fibroblasts, but the precise mechanisms of this process are not known. The cellular receptor for JSRV is hyaluronidase 2 (Hyal-2), the product of a putative tumor suppressor gene that in humans maps to a chromosomal region frequently deleted in the development of lung and breast cancers. Here we report studies to determine whether the Hyal-2-JSRV Env interaction plays a role in virus-induced transformation of rodent fibroblasts. Chimeric Env proteins between JSRV and the unrelated murine retroviruses Moloney murine leukemia virus (MMuLV) and mouse mammary tumor virus (MMTV) showed cell surface expression comparable to that of wild-type MMuLV Env and rescued infection of MMuLV particle pseudotypes. Interestingly, an MMuLV-JSRV chimera in which the putative receptor binding domain (RBD) and proline-rich region (PRR) of JSRV Env were replaced by the RBD and PRR of MMuLV induced transformation of 208F, a rodent fibroblast line. Cell lines derived from foci of MMuLV-JSRV chimeratransformed 208F cells grew in soft agar and showed Akt activation, a hallmark of JSRV-transformed rodent fibroblasts. Transformation assays performed using proteins with amino-terminal deletion mutations showed that the carboxy-terminal 141 amino acids of the transmembrane subunit (TM) were sufficient to induce cell transformation when targeted to the membrane with a myristoylation signal. Thus, the JSRV TM is necessary and sufficient to transform rodent fibroblasts. Taken together these results indicate that the interaction with Hyal-2 at least is not an essential determinant of JSRV-induced transformation of fibroblasts and that the viral TM functions essentially as an oncoprotein.

AB - Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). Expression of the JSRV envelope protein (Env) is sufficient to transform immortalized and primary fibroblasts, but the precise mechanisms of this process are not known. The cellular receptor for JSRV is hyaluronidase 2 (Hyal-2), the product of a putative tumor suppressor gene that in humans maps to a chromosomal region frequently deleted in the development of lung and breast cancers. Here we report studies to determine whether the Hyal-2-JSRV Env interaction plays a role in virus-induced transformation of rodent fibroblasts. Chimeric Env proteins between JSRV and the unrelated murine retroviruses Moloney murine leukemia virus (MMuLV) and mouse mammary tumor virus (MMTV) showed cell surface expression comparable to that of wild-type MMuLV Env and rescued infection of MMuLV particle pseudotypes. Interestingly, an MMuLV-JSRV chimera in which the putative receptor binding domain (RBD) and proline-rich region (PRR) of JSRV Env were replaced by the RBD and PRR of MMuLV induced transformation of 208F, a rodent fibroblast line. Cell lines derived from foci of MMuLV-JSRV chimeratransformed 208F cells grew in soft agar and showed Akt activation, a hallmark of JSRV-transformed rodent fibroblasts. Transformation assays performed using proteins with amino-terminal deletion mutations showed that the carboxy-terminal 141 amino acids of the transmembrane subunit (TM) were sufficient to induce cell transformation when targeted to the membrane with a myristoylation signal. Thus, the JSRV TM is necessary and sufficient to transform rodent fibroblasts. Taken together these results indicate that the interaction with Hyal-2 at least is not an essential determinant of JSRV-induced transformation of fibroblasts and that the viral TM functions essentially as an oncoprotein.

UR - http://www.scopus.com/inward/record.url?scp=0038027024&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038027024&partnerID=8YFLogxK

U2 - 10.1128/JVI.77.11.6341-6350.2003

DO - 10.1128/JVI.77.11.6341-6350.2003

M3 - Article

VL - 77

SP - 6341

EP - 6350

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 11

ER -