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Mechanism of cell entry and transformation by enzootic nasal tumor virus

Clarissa Dirks1, Fuh-Mei Duh, Sharath K Rai

  • 1Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.

Journal of Virology
|February 12, 2002
PubMed

Insights

Enzootic nasal tumor virus (ENTV) and jaagsiekte sheep retrovirus (JSRV) use the same receptor, Hyal2, to infect cells. Their envelope proteins transform cells, but distinct viral gene expression drives tissue-specific cancers in sheep.

Area of Science:

  • Virology
  • Oncology
  • Molecular Biology

Background:

  • Enzootic nasal tumor virus (ENTV) causes nasal tumors in sheep, while jaagsiekte sheep retrovirus (JSRV) causes lung cancer.
  • Both are simple retroviruses lacking known oncogenes, suggesting their envelope proteins are key to cancer development.

Purpose of the Study:

  • To investigate the oncogenic potential of the ENTV envelope (Env) protein.
  • To identify the cellular receptor for ENTV and compare it with JSRV.
  • To elucidate the mechanisms behind tissue-specific oncogenesis by these related viruses.

Main Methods:

  • Cell transformation assays using ENTV Env protein.
  • Virus entry studies using different cell lines and species.
  • Identification and cloning of ovine Hyal2 cDNA.
  • Comparative analysis of ENTV and JSRV Env protein sequences and viral gene expression.

Main Results:

  • ENTV Env protein transforms cultured cells, similar to JSRV Env.
  • Both ENTV and JSRV Env proteins utilize the Hyal2 receptor for cell entry.
  • ENTV Env exhibits a more restricted species tropism than JSRV Env, allowing identification of key amino acid regions.
  • Ovine Hyal2 functions as an efficient receptor for both viruses.

Conclusions:

  • The Env proteins of ENTV and JSRV are likely responsible for oncogenesis via cell transformation.
  • Tissue-specific cancer induction by ENTV and JSRV is regulated at the level of viral gene expression, not cell entry.
  • Distinct transcriptional regulatory elements contribute to the different target tissues of these viruses.

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