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. 1997 Feb;71(2):1671–1678. doi: 10.1128/jvi.71.2.1671-1678.1997

Late expression of a beta chemokine homolog by murine cytomegalovirus.

M R MacDonald 1, X Y Li 1, H W Virgin 4th 1
PMCID: PMC191229  PMID: 8995698

Abstract

A gene (HJ1) present in murine cytomegalovirus (MCMV) encodes an open reading frame (ORF) whose predicted amino acid sequence shows homology to the beta (or C-C) class of chemotactic cytokines known as chemokines. The region of homology is located in the carboxyl-terminal portion of the 116-amino-acid ORF. A 0.9-kb RNA transcript corresponding to the HJ1 gene is expressed in MCMV-infected fibroblasts and macrophages as a member of the late kinetic class of virally encoded transcripts. A transcriptional start site is located between the third and fourth methionine residues in the ORF, predicting a primary amino acid structure, starting at the fourth methionine residue, which includes a possible signal peptide as well as conserved cysteine residues typical for mammalian beta chemokines. The RNA transcript is polyadenylated, suggesting that it can undergo translation within the cytoplasm of an MCMV-infected cell. We speculate that expression of the chemokine homolog at late times in the MCMV replication cycle plays a role in MCMV pathogenesis, possibly by action as a chemotactic agonist or antagonist or by alteration of the activation or differentiation state of a susceptible cell such as a macrophage.

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Selected References

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  1. Ahuja S. K., Murphy P. M. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. J Biol Chem. 1993 Oct 5;268(28):20691–20694. [PubMed] [Google Scholar]
  2. Albrecht J. C., Nicholas J., Biller D., Cameron K. R., Biesinger B., Newman C., Wittmann S., Craxton M. A., Coleman H., Fleckenstein B. Primary structure of the herpesvirus saimiri genome. J Virol. 1992 Aug;66(8):5047–5058. doi: 10.1128/jvi.66.8.5047-5058.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alkhatib G., Combadiere C., Broder C. C., Feng Y., Kennedy P. E., Murphy P. M., Berger E. A. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996 Jun 28;272(5270):1955–1958. doi: 10.1126/science.272.5270.1955. [DOI] [PubMed] [Google Scholar]
  4. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  5. Baggiolini M., Dewald B., Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179. [PubMed] [Google Scholar]
  6. Bale J. F., Jr, O'Neil M. E. Detection of murine cytomegalovirus DNA in circulating leukocytes harvested during acute infection of mice. J Virol. 1989 Jun;63(6):2667–2673. doi: 10.1128/jvi.63.6.2667-2673.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ben-Baruch A., Michiel D. F., Oppenheim J. J. Signals and receptors involved in recruitment of inflammatory cells. J Biol Chem. 1995 May 19;270(20):11703–11706. doi: 10.1074/jbc.270.20.11703. [DOI] [PubMed] [Google Scholar]
  8. Boss J. M., Laster S. M., Gooding L. R. Sensitivity to tumour necrosis factor-mediated cytolysis is unrelated to manganous superoxide dismutase messenger RNA levels among transformed mouse fibroblasts. Immunology. 1991 Jul;73(3):309–315. [PMC free article] [PubMed] [Google Scholar]
  9. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchison C. A., 3rd, Kouzarides T., Martignetti J. A. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125–169. doi: 10.1007/978-3-642-74980-3_6. [DOI] [PubMed] [Google Scholar]
  10. Choe H., Farzan M., Sun Y., Sullivan N., Rollins B., Ponath P. D., Wu L., Mackay C. R., LaRosa G., Newman W. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996 Jun 28;85(7):1135–1148. doi: 10.1016/s0092-8674(00)81313-6. [DOI] [PubMed] [Google Scholar]
  11. Collins T. M., Quirk M. R., Jordan M. C. Biphasic viremia and viral gene expression in leukocytes during acute cytomegalovirus infection of mice. J Virol. 1994 Oct;68(10):6305–6311. doi: 10.1128/jvi.68.10.6305-6311.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. D'Aquila R. T., Summers W. C. Isolation and characterization of phosphonoacetic acid-resistant mutants of human cytomegalovirus. J Virol. 1987 Apr;61(4):1291–1295. doi: 10.1128/jvi.61.4.1291-1295.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Danielson P. E., Forss-Petter S., Brow M. A., Calavetta L., Douglass J., Milner R. J., Sutcliffe J. G. p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. DNA. 1988 May;7(4):261–267. doi: 10.1089/dna.1988.7.261. [DOI] [PubMed] [Google Scholar]
  14. Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., Di Marzio P., Marmon S., Sutton R. E., Hill C. M. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661–666. doi: 10.1038/381661a0. [DOI] [PubMed] [Google Scholar]
  15. Dragic T., Litwin V., Allaway G. P., Martin S. R., Huang Y., Nagashima K. A., Cayanan C., Maddon P. J., Koup R. A., Moore J. P. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun 20;381(6584):667–673. doi: 10.1038/381667a0. [DOI] [PubMed] [Google Scholar]
  16. Gao J. L., Murphy P. M. Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor. J Biol Chem. 1994 Nov 18;269(46):28539–28542. [PubMed] [Google Scholar]
  17. Gompels U. A., Nicholas J., Lawrence G., Jones M., Thomson B. J., Martin M. E., Efstathiou S., Craxton M., Macaulay H. A. The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology. 1995 May 10;209(1):29–51. doi: 10.1006/viro.1995.1228. [DOI] [PubMed] [Google Scholar]
  18. Heise M. T., Virgin H. W., 4th The T-cell-independent role of gamma interferon and tumor necrosis factor alpha in macrophage activation during murine cytomegalovirus and herpes simplex virus infections. J Virol. 1995 Feb;69(2):904–909. doi: 10.1128/jvi.69.2.904-909.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jones T. R., Muzithras V. P., Gluzman Y. Replacement mutagenesis of the human cytomegalovirus genome: US10 and US11 gene products are nonessential. J Virol. 1991 Nov;65(11):5860–5872. doi: 10.1128/jvi.65.11.5860-5872.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Keil G. M., Ebeling-Keil A., Koszinowski U. H. Immediate-early genes of murine cytomegalovirus: location, transcripts, and translation products. J Virol. 1987 Feb;61(2):526–533. doi: 10.1128/jvi.61.2.526-533.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Keil G. M., Ebeling-Keil A., Koszinowski U. H. Temporal regulation of murine cytomegalovirus transcription and mapping of viral RNA synthesized at immediate early times after infection. J Virol. 1984 Jun;50(3):784–795. doi: 10.1128/jvi.50.3.784-795.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lagenaur L. A., Manning W. C., Vieira J., Martens C. L., Mocarski E. S. Structure and function of the murine cytomegalovirus sgg1 gene: a determinant of viral growth in salivary gland acinar cells. J Virol. 1994 Dec;68(12):7717–7727. doi: 10.1128/jvi.68.12.7717-7727.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McGeoch D. J. On the predictive recognition of signal peptide sequences. Virus Res. 1985 Oct;3(3):271–286. doi: 10.1016/0168-1702(85)90051-6. [DOI] [PubMed] [Google Scholar]
  26. Mercer J. A., Marks J. R., Spector D. H. Molecular cloning and restriction endonuclease mapping of the murine cytomegalovirus genome (Smith Strain). Virology. 1983 Aug;129(1):94–106. doi: 10.1016/0042-6822(83)90398-7. [DOI] [PubMed] [Google Scholar]
  27. Miller M. D., Krangel M. S. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol. 1992;12(1-2):17–46. [PubMed] [Google Scholar]
  28. Neote K., DiGregorio D., Mak J. Y., Horuk R., Schall T. J. Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor. Cell. 1993 Feb 12;72(3):415–425. doi: 10.1016/0092-8674(93)90118-a. [DOI] [PubMed] [Google Scholar]
  29. Nicholas J. Determination and analysis of the complete nucleotide sequence of human herpesvirus. J Virol. 1996 Sep;70(9):5975–5989. doi: 10.1128/jvi.70.9.5975-5989.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
  31. Pollock J. L., Virgin H. W., 4th Latency, without persistence, of murine cytomegalovirus in the spleen and kidney. J Virol. 1995 Mar;69(3):1762–1768. doi: 10.1128/jvi.69.3.1762-1768.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Price P., Winter J. G., Shellam G. R. Genetically determined resistance to murine cytomegalovirus: a role for lymphocytostatic macrophages. J Gen Virol. 1987 Dec;68(Pt 12):2997–3008. doi: 10.1099/0022-1317-68-12-2997. [DOI] [PubMed] [Google Scholar]
  33. Rubin R. H. Impact of cytomegalovirus infection on organ transplant recipients. Rev Infect Dis. 1990 Sep-Oct;12 (Suppl 7):S754–S766. doi: 10.1093/clinids/12.supplement_7.s754. [DOI] [PubMed] [Google Scholar]
  34. Schooley R. T. Cytomegalovirus in the setting of infection with human immunodeficiency virus. Rev Infect Dis. 1990 Sep-Oct;12 (Suppl 7):S811–S819. doi: 10.1093/clinids/12.supplement_7.s811. [DOI] [PubMed] [Google Scholar]
  35. Selgrade M. K., Osborn J. E. Role of macrophages in resistance to murine cytomegalovirus. Infect Immun. 1974 Dec;10(6):1383–1390. doi: 10.1128/iai.10.6.1383-1390.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stoddart C. A., Cardin R. D., Boname J. M., Manning W. C., Abenes G. B., Mocarski E. S. Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus. J Virol. 1994 Oct;68(10):6243–6253. doi: 10.1128/jvi.68.10.6243-6253.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Thompson J. D., Higgins D. G., Gibson T. J. 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):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vieira J., Farrell H. E., Rawlinson W. D., Mocarski E. S. Genes in the HindIII J fragment of the murine cytomegalovirus genome are dispensable for growth in cultured cells: insertion mutagenesis with a lacZ/gpt cassette. J Virol. 1994 Aug;68(8):4837–4846. doi: 10.1128/jvi.68.8.4837-4846.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Winston D. J., Ho W. G., Champlin R. E. Cytomegalovirus infections after allogeneic bone marrow transplantation. Rev Infect Dis. 1990 Sep-Oct;12 (Suppl 7):S776–S792. doi: 10.1093/clinids/12.supplement_7.s776. [DOI] [PubMed] [Google Scholar]
  40. Woisetschlaeger M., Strominger J. L., Speck S. H. Mutually exclusive use of viral promoters in Epstein-Barr virus latently infected lymphocytes. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6498–6502. doi: 10.1073/pnas.86.17.6498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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