Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail.
The Syrian golden hamster (Mesocricetus auratus) is highly susceptible to a number of intracellular pathogens. Interferon-gamma (IFN-gamma), the primary macrophage-activating cytokine, plays a key role in the host defense against intracellular pathogens. The hamster IFN-gamma cDNA encodes a 174 amino acid protein that has an additional 17 amino acids at the carboxyl-terminus compared to IFN-gamma of mice and rats. A homologous C-terminal tail is also found in other non-murine rodents. The biological activity of hamster IFN-gamma had not been investigated previously so we first demonstrated the activity of native IFN-gamma in assays of IFN-gamma-induced receptor signaling and antiviral activity against vesicular stomatitis virus. We then tested the hypothesis that the C-terminal tail of hamster IFN-gamma could influence its biological activity. A truncated hamster IFN-gamma, 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-gamma antibodies specifically inhibited this biological activity. Collectively, these data indicate that this unique structural feature influences the biological activity of hamster IFN-gamma.
Zhao
Weiguo
W
Research Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System, 7400 Merton Minter Dr., Mailstop 151, San Antonio, TX 78229-4404, USA.
Valencia
Anais Z
AZ
Melby
Peter C
PC
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D010802:Phylogeny; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D011994:Recombinant Proteins; D007371:Interferon-gamma