+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus



Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus



Journal of Virology 66(2): 743-749



Transmissible gastroenteritis virus, an enteropathogenic coronavirus of swine, is a potent inducer of alpha interferon (IFN-alpha) both in vitro and in vivo. Previous studies have shown that virus-infected fixed cells or viral suspensions were able to induce an early and strong IFN-alpha synthesis by naive lymphocytes. Two monoclonal antibodies directed against the viral membrane glycoprotein M (29,000; formerly E1) were found to markedly inhibit virus-induced IFN production, thus assigning to M protein a potential effector role in this phenomenon (B. Charley and H. Laude, J. Virol. 62:8-11, 1988). The present report describes the selection and characterization of a collection of 125 mutant viruses which escaped complement-mediated neutralization by two IFN induction-blocking anti-M protein monoclonal antibodies. Two of these mutants, designated H92 and dm49-4, were found to exhibit a markedly reduced interferogenic activity. IFN synthesis by lymphocytes incubated with purified suspensions of these mutants was 30- to 300-fold lower than that of the parental virus. The transcription of IFN-alpha genes following induction by each mutant was decreased proportionally, as evidenced by Northern (RNA) blot analysis. The sequence of the M gene of 20 complement-mediated neutralization-resistant mutants, including the 2 defective mutants, was determined by direct sequencing of genome RNA. Thirteen distinct amino acid changes were predicted, all located at positions 6 to 22 from the N terminus of the mature M protein and within the putative ectodomain of the molecule. Two substitutions, Thr-17 to Ile and Ser-19 to Pro, were assumed to generate the defective phenotypes of mutants dm49-4 and H92, respectively. The alteration of an Asn-Ser-Thr sequence in dm49-4 virus led to the synthesis of an M protein devoid of a glycan side chain, which suggests a possible involvement of this structure in IFN induction. Overall, these data supported the view that an interferogenic determinant resides in the N-terminal, exposed part of the molecule and provided further evidence for the direct role of M protein in the induction of IFN-alpha by transmissible gastroenteritis virus. The acronym VIP (viral interferogenic protein) is proposed as a designation for this particular class of proteins.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 068543703

Download citation: RISBibTeXText

PMID: 1309909


Related references

Single amino acid changes in viral glycoprotein m affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus. Journal of Virology 66(2): 743-749, 1992

Induction of alpha interferon by transmissible gastroenteritis coronavirus: role of transmembrane glycoprotein E1. Journal of Virology 62(1): 8-11, 1988

Four major antigenic sites of the coronavirus transmissible gastroenteritis virus are located on the amino-terminal half of spike glycoprotein S. Journal of General Virology 71: 1313-1323, 1990

Coronavirus transmissible gastroenteritis virus-mediated induction of IFN alpha-mRNA in porcine leukocytes requires prior synthesis of soluble proteins. Veterinary Research 25(1): 29-36, 1994

Cellular immune responses of pigs after primary inoculation with porcine respiratory coronavirus or transmissible gastroenteritis virus and challenge with transmissible gastroenteritis virus. Veterinary Immunology & Immunopathology 48(1-2): 35-54, 1995

Characterization of blood mononuclear cells producing IFN alpha following induction by coronavirus-infected cells (porcine transmissible gastroenteritis virus). Research in Immunology 141(2): 141-151, 1990

Comparison of the antibody response to transmissible gastroenteritis virus and porcine respiratory coronavirus, using monoclonal antibodies to antigenic sites A and X of the S glycoprotein. American Journal of Veterinary Research 53(2): 184-190, 1992

Sequence and amino terminal processing of the transmembrane protein e1 of the coronavirus transmissible gastroenteritis virus. Journal of General Virology 68(6): 1687-1694, 1987

The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 Axis. Journal of Virology 92(22):, 2018

Induction of transmissible gastroenteritis coronavirus-neutralizing antibodies in vitro by virus-specific T helper cell hybridomas. Journal of General Virology 70: 659-672, 1989

Induction of protective immunity against transmissible gastroenteritis virus after exposure of neonatal pigs to porcine respiratory coronavirus. American Journal of Veterinary Research 57(2): 157-162, 1996

Cooperation between transmissible gastroenteritis coronavirus (TGEV) structural proteins in the in vitro induction of virus-specific antibodies. Virus Research 46(1-2): 111-124, 1996

Differentiation of transmissible gastroenteritis virus from porcine respiratory coronavirus and other antigenically related coronaviruses by using cDNA probes specific for the 5' region of the S glycoprotein gene. Journal of Clinical Microbiology 29(1): 215-218, 1991

Studies on transmissible gastroenteritis of swine. 3. The effect of selective inhibitors of viral replication on a cytopathogenic virus from transmissible gastroenteritis. Canadian Journal of Comparative Medicine and Veterinary Science 31(11): 299-302, 1967

Studies on transmissible gastroenteritis of swine III. The effect of selective inhibitors of viral replication on a cytopathogenic virus from transmissible gastroenteritis. Can. J. comp. Med 31: 299-302, 1967