Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail

Weiguo Zhao, Anais Z. Valencia, Peter Melby

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The Syrian golden hamster (Mesocricetus auratus) is highly susceptible to a number of intracellular pathogens. Interferon-gamma (IFN-γ), the primary macrophage-activating cytokine, plays a key role in the host defense against intracellular pathogens. The hamster IFN-γ cDNA encodes a 174 amino acid protein that has an additional 17 amino acids at the carboxyl-terminus compared to IFN-γ of mice and rats. A homologous C-terminal tail is also found in other non-murine rodents. The biological activity of hamster IFN-γ had not been investigated previously so we first demonstrated the activity of native IFN-γ in assays of IFN-γ-induced receptor signaling and antiviral activity against vesicular stomatitis virus. We then tested the hypothesis that the C-terminal tail of hamster IFN-γ could influence its biological activity. A truncated hamster IFN-γ, in which the C-terminal 17 aa were removed by insertion of a stop codon at the position corresponding to the stop codon in the mouse sequence, had approximately 10-fold greater activity than the full length protein when measured in the two bioassays. Polyclonal and monoclonal anti-hamster IFN-γ antibodies specifically inhibited this biological activity. Collectively, these data indicate that this unique structural feature influences the biological activity of hamster IFN-γ.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalCytokine
Volume34
Issue number5-6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Bioactivity
Cricetinae
Interferon-gamma
Tail
Terminator Codon
Mesocricetus
Pathogens
Amino Acids
Vesicular Stomatitis
Bioassay
Macrophages
Biological Assay
Antiviral Agents
Viruses
Rodentia
Proteins
Rats
Complementary DNA
Assays
Cytokines

Keywords

  • Antiviral
  • Hamster
  • Interferon-gamma
  • Mesocricetus auratus

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail. / Zhao, Weiguo; Valencia, Anais Z.; Melby, Peter.

In: Cytokine, Vol. 34, No. 5-6, 06.2006, p. 243-251.

Research output: Contribution to journalArticle

Zhao, Weiguo ; Valencia, Anais Z. ; Melby, Peter. / Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail. In: Cytokine. 2006 ; Vol. 34, No. 5-6. pp. 243-251.
@article{2476df41fad4474d8e0bae08bdd7c9df,
title = "Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail",
abstract = "The Syrian golden hamster (Mesocricetus auratus) is highly susceptible to a number of intracellular pathogens. Interferon-gamma (IFN-γ), the primary macrophage-activating cytokine, plays a key role in the host defense against intracellular pathogens. The hamster IFN-γ cDNA encodes a 174 amino acid protein that has an additional 17 amino acids at the carboxyl-terminus compared to IFN-γ of mice and rats. A homologous C-terminal tail is also found in other non-murine rodents. The biological activity of hamster IFN-γ had not been investigated previously so we first demonstrated the activity of native IFN-γ in assays of IFN-γ-induced receptor signaling and antiviral activity against vesicular stomatitis virus. We then tested the hypothesis that the C-terminal tail of hamster IFN-γ could influence its biological activity. A truncated hamster IFN-γ, in which the C-terminal 17 aa were removed by insertion of a stop codon at the position corresponding to the stop codon in the mouse sequence, had approximately 10-fold greater activity than the full length protein when measured in the two bioassays. Polyclonal and monoclonal anti-hamster IFN-γ antibodies specifically inhibited this biological activity. Collectively, these data indicate that this unique structural feature influences the biological activity of hamster IFN-γ.",
keywords = "Antiviral, Hamster, Interferon-gamma, Mesocricetus auratus",
author = "Weiguo Zhao and Valencia, {Anais Z.} and Peter Melby",
year = "2006",
month = "6",
doi = "10.1016/j.cyto.2006.05.006",
language = "English (US)",
volume = "34",
pages = "243--251",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "5-6",

}

TY - JOUR

T1 - Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail

AU - Zhao, Weiguo

AU - Valencia, Anais Z.

AU - Melby, Peter

PY - 2006/6

Y1 - 2006/6

N2 - The Syrian golden hamster (Mesocricetus auratus) is highly susceptible to a number of intracellular pathogens. Interferon-gamma (IFN-γ), the primary macrophage-activating cytokine, plays a key role in the host defense against intracellular pathogens. The hamster IFN-γ cDNA encodes a 174 amino acid protein that has an additional 17 amino acids at the carboxyl-terminus compared to IFN-γ of mice and rats. A homologous C-terminal tail is also found in other non-murine rodents. The biological activity of hamster IFN-γ had not been investigated previously so we first demonstrated the activity of native IFN-γ in assays of IFN-γ-induced receptor signaling and antiviral activity against vesicular stomatitis virus. We then tested the hypothesis that the C-terminal tail of hamster IFN-γ could influence its biological activity. A truncated hamster IFN-γ, in which the C-terminal 17 aa were removed by insertion of a stop codon at the position corresponding to the stop codon in the mouse sequence, had approximately 10-fold greater activity than the full length protein when measured in the two bioassays. Polyclonal and monoclonal anti-hamster IFN-γ antibodies specifically inhibited this biological activity. Collectively, these data indicate that this unique structural feature influences the biological activity of hamster IFN-γ.

AB - The Syrian golden hamster (Mesocricetus auratus) is highly susceptible to a number of intracellular pathogens. Interferon-gamma (IFN-γ), the primary macrophage-activating cytokine, plays a key role in the host defense against intracellular pathogens. The hamster IFN-γ cDNA encodes a 174 amino acid protein that has an additional 17 amino acids at the carboxyl-terminus compared to IFN-γ of mice and rats. A homologous C-terminal tail is also found in other non-murine rodents. The biological activity of hamster IFN-γ had not been investigated previously so we first demonstrated the activity of native IFN-γ in assays of IFN-γ-induced receptor signaling and antiviral activity against vesicular stomatitis virus. We then tested the hypothesis that the C-terminal tail of hamster IFN-γ could influence its biological activity. A truncated hamster IFN-γ, in which the C-terminal 17 aa were removed by insertion of a stop codon at the position corresponding to the stop codon in the mouse sequence, had approximately 10-fold greater activity than the full length protein when measured in the two bioassays. Polyclonal and monoclonal anti-hamster IFN-γ antibodies specifically inhibited this biological activity. Collectively, these data indicate that this unique structural feature influences the biological activity of hamster IFN-γ.

KW - Antiviral

KW - Hamster

KW - Interferon-gamma

KW - Mesocricetus auratus

UR - http://www.scopus.com/inward/record.url?scp=33747123288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747123288&partnerID=8YFLogxK

U2 - 10.1016/j.cyto.2006.05.006

DO - 10.1016/j.cyto.2006.05.006

M3 - Article

VL - 34

SP - 243

EP - 251

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 5-6

ER -