Home LiteratureArticle Details
PMID: 9499096 Published · ppublish English Journal Article

The R33 G protein-coupled receptor gene of rat cytomegalovirus plays an essential role in the pathogenesis of viral infection.

Journal of virology ·Vol. 72 ·No. 3 ·1998-03-00 ·Pages 2352-63

Beisser PS, Vink C, Van Dam JG, Grauls G, Vanherle SJ, Bruggeman CA

Abstract

We have identified a rat cytomegalovirus (RCMV) gene that encodes a G-protein-coupled receptor (GCR) homolog. This gene (R33) belongs to a family that includes the human cytomegalovirus UL33 gene. R33 was found to be transcribed during the late phase of RCMV infection in rat embryo fibroblasts. Unlike the mRNAs from all the other members of the UL33 family that have been studied to date, the R33 mRNA is not spliced. To study the function of the R33 gene, we constructed an RCMV strain in which the R33 open reading frame is disrupted. The mutant strain (RCMV deltaR33) did not show differences in replication from wild-type RCMV upon infection of several rat cell types in vitro. However, marked differences were seen between the mutant and wild-type strain in the pathogenesis of infection in immunocompromised rats. First, the mutant strain induced a significantly lower mortality than the wild-type virus did. Second, in contrast to wild-type RCMV, the mutant strain did not efficiently replicate in the salivary gland epithelial cells of immunocompromised rats. Although viral DNA was detected in salivary glands of RCMV deltaR33-infected rats up to 14 days postinfection, it could not be detected at later time points. This indicates that although the strain with R33 deleted is probably transported to the salivary glands in a similar fashion to that for wild-type virus, the mutant virus is not able to either enter or replicate in salivary gland epithelial cells. We conclude that the RCMV R33 gene plays a vital role in the pathogenesis of infection.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Line Cloning, Molecular Cytomegalovirus/genetics,pathogenicity,physiology DNA, Viral GTP-Binding Proteins/metabolism Gene Deletion Genes, Viral Humans Molecular Sequence Data Mutagenesis RNA, Viral Rats Receptors, Cell Surface/genetics,metabolism Receptors, G-Protein-Coupled Sequence Homology, Amino Acid Transcription, Genetic Viral Proteins/genetics,metabolism Virus Replication
Chemicals
DNA, Viral R33 protein, rat cytomegalovirus RNA, Viral Receptors, Cell Surface Receptors, G-Protein-Coupled Viral Proteins GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Beisser P S
Department of Medical Microbiology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Vink C
Van Dam J G
Grauls G
Vanherle S J
Bruggeman C A
References (53)
53 references, click to expand
  1. A dual role for endothelial cells in cytomegalovirus infection? A study of cytomegalovirus infection in a series of rat endothelial cell lines.
    Virus Res. 1996 Dec;46(1-2):65-74 PMID: 9029778
  2. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
    Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 PMID: 7984417
  3. Amino acid sequence of bacteriorhodopsin.
    Proc Natl Acad Sci U S A. 1979 Oct;76(10):5046-50 PMID: 291920
  4. Isolation of a cytomegalovirus-like agent from wild rats.
    Arch Virol. 1982;73(3-4):231-41 PMID: 6293414
  5. DNA sequence and expression of the B95-8 Epstein-Barr virus genome.
    Nature. 1984 Jul 19-25;310(5974):207-11 PMID: 6087149
  6. Isolation and nucleotide sequence of the gene encoding human rhodopsin.
    Proc Natl Acad Sci U S A. 1984 Aug;81(15):4851-5 PMID: 6589631
  7. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3.
    Immunology. 1985 Mar;54(3):589-99 PMID: 3882559
  8. Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1.
    Immunology. 1994 Sep;83(1):140-7 PMID: 7821959
  9. Sequence analysis of HindIII Q2 fragment of capripoxvirus reveals a putative gene encoding a G-protein-coupled chemokine receptor homologue.
    Virology. 1995 May 10;209(1):207-12 PMID: 7747471
  10. The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution.
    Virology. 1995 May 10;209(1):29-51 PMID: 7747482
  11. The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity.
    Biochem Biophys Res Commun. 1995 Jun 6;211(1):325-30 PMID: 7540006
  12. The DNA sequence of equine herpesvirus 2.
    J Mol Biol. 1995 Jun 9;249(3):520-8 PMID: 7783207
  13. Expression cloning and chromosomal mapping of the leukocyte activation antigen CD97, a new seven-span transmembrane molecule of the secretion receptor superfamily with an unusual extracellular domain.
    J Immunol. 1995 Aug 15;155(4):1942-50 PMID: 7636245
  14. Molecular cloning of a putative Ca(2+)-sensing receptor cDNA from human kidney.
    Biochem Biophys Res Commun. 1995 Sep 14;214(2):524-9 PMID: 7677761
  15. Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism.
    J Virol. 1996 Mar;70(3):1365-74 PMID: 8627652
  16. Determination and analysis of the complete nucleotide sequence of human herpesvirus.
    J Virol. 1996 Sep;70(9):5975-89 PMID: 8709220
  17. Cloning and sequence analysis of the genes encoding DNA polymerase, glycoprotein B, ICP18.5 and major DNA-binding protein of rat cytomegalovirus.
    J Gen Virol. 1996 Jul;77 ( Pt 7):1559-62 PMID: 8757999
  18. Structure of the rat cytomegalovirus genome termini.
    J Virol. 1996 Aug;70(8):5221-9 PMID: 8764031
  19. Kaposi's sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi's sarcoma and malignant lymphoma.
    J Virol. 1996 Nov;70(11):8218-23 PMID: 8892957
  20. Identification of the human cytomegalovirus G protein-coupled receptor homologue encoded by UL33 in infected cells and enveloped virus particles.
    Virology. 1996 Nov 1;225(1):111-25 PMID: 8918538
  21. Analysis of the complete DNA sequence of murine cytomegalovirus.
    J Virol. 1996 Dec;70(12):8833-49 PMID: 8971012
  22. Identification and characterization of a G protein-coupled receptor homolog encoded by murine cytomegalovirus.
    J Virol. 1997 Feb;71(2):1521-9 PMID: 8995678
  23. Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation.
    Nature. 1997 Jan 23;385(6614):347-50 PMID: 9002520
  24. Masters of deception: a review of herpesvirus immune evasion strategies.
    Immunol Cell Biol. 1996 Dec;74(6):513-22 PMID: 8989589
  25. Biology of rat cytomegalovirus infection.
    Intervirology. 1985;24(1):1-9 PMID: 2995270
  26. The yeast alpha-factor receptor: structural properties deduced from the sequence of the STE2 gene.
    Nucleic Acids Res. 1985 Dec 9;13(23):8463-75 PMID: 3001640
  27. Molecular cloning and restriction endonuclease mapping of the rat cytomegalovirus genome.
    J Gen Virol. 1986 Jul;67 ( Pt 7):1327-42 PMID: 3014047
  28. The development and characterization of monoclonal antibodies against rat cytomegalovirus induced antigens.
    Arch Virol. 1987;94(1-2):55-70 PMID: 2437886
  29. Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor.
    Nucleic Acids Res. 1987 Dec 23;15(24):10604 PMID: 3697105
  30. Optimal alignments in linear space.
    Comput Appl Biosci. 1988 Mar;4(1):11-7 PMID: 3382986
  31. A chemoattractant receptor controls development in Dictyostelium discoideum.
    Science. 1988 Sep 16;241(4872):1467-72 PMID: 3047871
  32. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes.
    J Exp Med. 1989 Jan 1;169(1):73-86 PMID: 2783336
  33. Monoclonal antibody to a triggering structure expressed on rat natural killer cells and adherent lymphokine-activated killer cells.
    J Exp Med. 1989 Apr 1;169(4):1373-89 PMID: 2466943
  34. Rapid and sensitive sequence comparison with FASTP and FASTA.
    Methods Enzymol. 1990;183:63-98 PMID: 2156132
  35. Human cytomegalovirus encodes three G protein-coupled receptor homologues.
    Nature. 1990 Apr 19;344(6268):774-7 PMID: 2158627
  36. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169.
    Curr Top Microbiol Immunol. 1990;154:125-69 PMID: 2161319
  37. An animal model for therapeutic intervention studies of CMV infection in the immunocompromised host.
    Arch Virol. 1990;114(1-2):91-107 PMID: 2171466
  38. Cloning and sequencing of human FSH receptor cDNA.
    Biochem Biophys Res Commun. 1991 Mar 29;175(3):1125-30 PMID: 1709010
  39. Cytomegalovirus homologs of cellular G protein-coupled receptor genes are transcribed.
    J Virol. 1991 Jul;65(7):3915-8 PMID: 1645799
  40. Molecular cloning and sequencing of a cDNA encoding a human alpha 1A adrenergic receptor.
    Biochem Biophys Res Commun. 1991 Sep 30;179(3):1485-90 PMID: 1656955
  41. Herpesvirus saimiri encodes homologues of G protein-coupled receptors and cyclins.
    Nature. 1992 Jan 23;355(6358):362-5 PMID: 1309943
  42. Sequence alignment of the G-protein coupled receptor superfamily.
    DNA Cell Biol. 1992 Jan-Feb;11(1):1-20 PMID: 1310857
  43. Cytomegalovirus determinant of replication in salivary glands.
    J Virol. 1992 Jun;66(6):3794-802 PMID: 1316482
  44. Characterization of a strain of murine cytomegalovirus which fails to grow in the salivary glands of mice.
    J Gen Virol. 1992 Aug;73 ( Pt 8):2021-9 PMID: 1322959
  45. Differential thymus dependence of rat CD8 isoform expression.
    Eur J Immunol. 1992 Nov;22(11):2841-8 PMID: 1358623
  46. Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor.
    J Exp Med. 1993 May 1;177(5):1421-7 PMID: 7683036
  47. Cytomegalovirus induces class II expression in rat heart endothelial cells.
    J Heart Lung Transplant. 1993 Jul-Aug;12(4):644-51 PMID: 8396436
  48. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri.
    J Biol Chem. 1993 Oct 5;268(28):20691-4 PMID: 8407886
  49. DNA sequence analysis of conserved and unique regions of swinepox virus: identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue.
    Virology. 1993 Dec;197(2):511-28 PMID: 8249275
  50. Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus.
    J Virol. 1994 Oct;68(10):6243-53 PMID: 8083964
  51. CMV-induced class II antigen expression in various rat organs.
    Transpl Int. 1994 Jul;7(4):302-8 PMID: 7916933
  52. Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor.
    J Biol Chem. 1994 Nov 18;269(46):28539-42 PMID: 7961796
  53. Infection with rat cytomegalovirus (CMV) in the immunocompromised host is associated with the appearance of a T cell population with reduced CD8 and T cell receptor (TCR) expression.
    Clin Exp Immunol. 1997 Dec;110(3):349-57 PMID: 9409635
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.3.2352-2363.1998
Published
1998-03-00
Pages
2352-63
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC109535
Subset
IM
Databases
GENBANK
U91788
External Links
PubMed source DOI: 10.1128/JVI.72.3.2352-2363.1998 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2