Systematic mutagenesis of the murine gammaherpesvirus 68 M2 protein identifies domains important for chronic infection

Journal of Virology

Volumn 82, Issue 7, 2008, Pages 3295-3310

  Herskowitz, Jeremy H ^a   Siegel, Andrea M ^a   Jacoby, Meagan A ^a   Speck, Samuel H ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN M2; TYROSINE; VAV PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; B LYMPHOCYTE; CARBOXY TERMINAL SEQUENCE; CELL STRAIN COS1; CHRONIC DISEASE; CLUSTER ANALYSIS; CONTROLLED STUDY; EMBRYO; FEMALE; GENE DISRUPTION; HERPES VIRUS; MOUSE; MURINE GAMMA HERPES VIRUS 68; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN MOTIF; SIGNAL TRANSDUCTION; SPLEEN CELL; TISSUE CULTURE; VIRUS INFECTION; VIRUS MUTANT; VIRUS MUTATION; VIRUS REACTIVATION; VIRUS RECOMBINANT;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMALS; B-LYMPHOCYTES; FEMALE; GRB2 ADAPTOR PROTEIN; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LUNG; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; PLAQUE ASSAY; PROTEIN BINDING; RHADINOVIRUS; SPLEEN; VIRAL PROTEINS; VIRUS ACTIVATION; VIRUS LATENCY; VIRUS REPLICATION;

ANIMALIA; CALOCA; HUMAN HERPESVIRUS 4; MURINAE; MUS;

EID: 41149122053     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.02234-07     Document Type: Article

References (64)

1. Adler, B., E. Schaadt, B. Kempkes, U. Zimber-Strobl, B. Baier, and G. W. Bornkamm. 2002. Control of Epstein-Barr virus reactivation by activated CD40 and viral latent membrane protein 1. Proc. Natl. Acad. Sci. USA 99:437-442.
2. Adler, H., M. Messerle, M. Wagner, and U. H. Koszinowski. 2000. Cloning and mutagenesis of the murine gammaherpesvirus 68 genome as an infectious bacterial artificial chromosome. J. Virol. 74:6964-6974.
3. Ahn, J. W., K. L. Powell, P. Kellam, and D. G. Alber. 2002. Gammaherpesvirus lytic gene expression as characterized by DNA array. J. Virol. 76: 6244-6256.
4. Babcock, G. J., D. Hochberg, and A. D. Thorley-Lawson. 2000. The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 13:497-506.
5. Beaufils, P., D. Choquet, R. Z. Mamoun, and B. Malissen. 1993. The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein 2A can elicit early and late lymphocyte activation events. EMBO J. 12:5105-5112.
6. Blaskovic, D., M. Stancekova, J. Svobodova, and J. Mistrikova. 1980. Isolation of five strains of herpesviruses from two species of free living small rodents. Acta Virol. 24:468.
7. Burkhardt, A. L., J. B. Bolen, E. Kieff, and R. Longnecker. 1992. An Epstein-Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases. J. Virol. 66:5161-5167.
8. Caldwell, R. G., J. B. Wilson, S. J. Anderson, and R. Longnecker. 1998. Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9:405-411.
9. Choi, J. K., B. S. Lee, S. N. Shim, M. Li, and J. U. Jung. 2000. Identification of the novel K15 gene at the rightmost end of the Kaposi's sarcoma-associated herpesvirus genome. J. Virol. 74:436-446.
10. Clambey, E. T., H. W. Virgin IV, and S. H. Speck. 2002. Characterization of a spontaneous 9.5-kilobase-deletion mutant of murine gammaherpesvirus 68 reveals tissue-specific genetic requirements for latency. J. Virol. 76:6532-6544.
11. Damania, B., J. K. Choi, and J. U. Jung. 2000. Signaling activities of gammaherpesvirus membrane proteins. J. Virol. 74:1593-1601.
12. Doherty, P. C., J. P. Christensen, G. T. Belz, P. G. Stevenson, and M. Y. Sangster. 2001. Dissecting the host response to a gamma-herpesvirus. Philos. Trans. R. Soc. Lond. B 356:581-593.
13. Doherty, P. C., R. A. Tripp, A. M. Hamilton-Easton, R. D. Cardin, D. L. Woodland, and M. A. Blackman. 1997. Tuning into immunological dissonance: an experimental model for infectious mononucleosis. Curr. Opin. Immunol. 9:477-483.
14. Efstathiou, S., Y. M. Ho, S. Hall, C. J. Styles, S. D. Scott, and U. A. Gompels. 1990. Murine herpesvirus 68 is genetically related to the gammaherpesviruses Epstein-Barr virus and herpesvirus saimiri. J. Gen. Virol. 71:1365-1372.
15. Fruehling, S., and R. Longnecker. 1997. The immunoreceptor tyrosine-based activation motif of Epstein-Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Virology 235:241-251.
16. Glenn, M., L. Rainbow, F. Aurade, A. Davison, and T. F. Schulz. 1999. Identification of a spliced gene from Kaposi's sarcoma-associated herpesvirus encoding a protein with similarities to latent membrane proteins 1 and 2A of Epstein-Barr virus. J. Virol. 73:6953-6963.
17. Herskowitz, J., M. A. Jacoby, and S. H. Speck. 2005. The murine gammaherpesvirus 68 M2 gene is required for efficient reactivation from latently infected B cells. J. Virol. 79:2261-2273.
18. Husain, S. M., E. J. Usherwood, H. Dyson, C. Coleclough, M. A. Coppola, D. L. Woodland, M. A. Blackman, J. P. Stewart, and J. T. Sample. 1999. Murine gammaherpesvirus M2 gene is latency-associated and its protein a target for CD8(+) T lymphocytes. Proc. Natl. Acad. Sci. USA 96:7508-7513.
19. Jacoby, M. A., H. W. Virgin IV, and S. H. Speck. 2002. Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation. J. Virol. 76:1790-1801.
20. Jung, J. U., S. M. Lang, U. Friedrich, T. Jun, T. M. Roberts, R. C. Desrosiers, and B. Biesinger. 1995. Identification of Lck-binding elements in tip of herpesvirus saimiri. J. Biol. Chem. 270:20660-20667.
21. Jung, J. U., S. M. Lang, T. Jun, T. M. Roberts, A. Veillette, and R. C. Desrosiers. 1995. Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. J. Virol. 69:7814-7822.
22. Kilger, E., A. Kieser, M. Baumann, and W. Hammerschmidt. 1998. Epstein-Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J. 17:1700-1709.
23. Lagunoff, M., R. Majeti, A. Weiss, and D. Ganem. 1999. Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus. Proc. Natl. Acad. Sci. USA 96:5704-5709.
24. Lee, H., J. Guo, M. Li, J. K. Choi, M. DeMaria, M. Rosenzweig, and J. U. Jung. 1998. Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus. Mol. Cell. Biol. 18:5219-5228.
25. Liang, X., M. T. Pickering, N. H. Cho, H. Chang, M. R. Volkert, T. F. Kowalik, and J. U. Jung. 2006. Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2. J. Virol. 80:5862-5874.
26. Liang, X., Y. C. Shin, R. E. Means, and J. U. Jung. 2004. Inhibition of interferon-mediated antiviral activity by murine gammaherpesvirus 68 latency-associated M2 protein. J. Virol. 78:12416-12427.
27. Longnecker, R., B. Druker, T. M. Roberts, and E. Kieff. 1991. An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase. J. Virol. 65:3681-3692.
28. Longnecker, R., M. Merchant, M. E. Brown, S. Fruehling, J. O. Bickford, M. Ikeda, and R. N. Harty. 2000. WW- and SH3-domain interactions with Epstein-Barr virus LMP2A. Exp. Cell Res. 257:332-340.
29. Macrae, A. I., E. J. Usherwood, S. M. Husain, E. Flano, I. J. Kim, D. L. Woodland, A. A. Nash, M. A. Blackman, J. T. Sample, and J. P. Stewart. 2003. Murid herpesvirus 4 strain 68 M2 protein is a B-cell-associated antigen important for latency but not lymphocytosis. J. Virol. 77:9700-9709.
30. Madureira, P. A., P. Matos, I. Soeiro, L. K. Dixon, J. P. Simas, and E. W. Lam. 2005. Murine gamma-herpesvirus 68 latency protein M2 binds to Vav signaling proteins and inhibits B-cell receptor-induced cell cycle arrest and apoptosis in WEHI-231 B cells. J. Biol. Chem. 280:37310-37318.
31. Martinez-Guzman, D., T. Rickabaugh, T. T. Wu, H. Brown, S. Cole, M. J. Song, L. Tong, and R. Sun. 2003. Transcription program of murine gammaherpesvirus 68. J. Virol. 77:10488-10503.
32. Mistrikova, J., and D. Blaskovic. 1985. Ecology of the murine alphaherpesvirus and its isolation from lungs of rodents in cell culture. Acta Virol. 29:312-317.
33. Moorman, N. J., D. O. Willer, and S. H. Speck. 2003. The Gammaherpesvirus 68 Latency-Associated Nuclear Antigen Homolog Is Critical for the Establishment of Splenic Latency. J. Virol. 77:10295-10303.
34. Moser, J. M., J. W. Upton, R. D. Allen III, C. B. Wilson, and S. H. Speck. 2005. Role of B-cell proliferation in the establishment of gammaherpesvirus latency. J. Virol. 79:9480-9491.
35. Nash, A. A., B. M. Dutia, J. P. Stewart, and A. J. Davison. 2001. Natural history of murine gamma-herpesvirus infection. Philos. Trans. R. Soc. Lond. B 356:569-579.
36. Nash, A. A., and N. P. Sunil-Chandra. 1994. Interactions of the murine gammaherpesvirus with the immune system. Curr. Opin. Immunol. 6:560-563.
37. Petrelli, A., G. F. Gilestro, S. Lanzardo, P. M. Comoglio, N. Migone, and S. Giordano. 2002. The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature 416:187-190.
38. Pollock, J. L., and H. W. Virgin IV. 1995. Latency, without persistence, of murine cytomegalovirus in the spleen and kidney. J. Virol. 69:1762-1768.
39. Poole, L. J., J. C. Zong, D. M. Ciufo, D. J. Alcendor, J. S. Cannon, R. Ambinder, J. M. Orenstein, M. S. Reitz, and G. S. Hayward. 1999. Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi's sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end. J. Virol. 73:6646-6660.
40. Rajcani, J., D. Blaskovic, J. Svobodova, F. Ciampor, D. Huckova, and D. Stanekova. 1985. Pathogenesis of acute and persistent murine herpesvirus infection in mice. Acta Virol. 29:51-60.
41. Reutens, A. T., and C. G. Begley. 2002. Endophilin-1: a multifunctional protein. Int. J. Biochem. Cell Biol. 34:1173-1177.
42. Ringstad, N., H. Gad, P. Low, G. Di Paolo, L. Brodin, O. Shupliakov, and P. De Camilli. 1999. Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron 24: 143-154.
43. Rodrigues, L., M. Pires de Miranda, M. J. Caloca, X. R. Bustelo, and J. P. Simas. 2006. Activation of Vav by the gammaherpesvirus M2 protein contributes to the establishment of viral latency in B lymphocytes. J. Virol. 80:6123-6135.
44. Scholle, F., R. Longnecker, and N. Raab-Traub. 1999. Epithelial cell adhesion to extracellular matrix proteins induces tyrosine phosphorylation of the Epstein-Barr virus latent membrane protein 2: a role for C-terminal Src kinase. J. Virol. 73:4767-4775.
45. Simas, J. P., and S. Efstathiou. 1998. Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis. Trends Microbiol. 6:276-282.
46. Smith, G. A., and L. W. Enquist. 1999. Construction and transposon mutagenesis in Escherichia coli of a full-length infectious clone of pseudorabies virus, an alphaherpesvirus. J. Virol. 73:6405-6414.
47. Soubeyran, P., K. Kowanetz, I. Szymkiewicz, W. Y. Langdon, and I. Dikic. 2002. Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature 416:183-187.
48. Speck, S. H., and H. W. Virgin. 1999. Host and viral genetics of chronic infection: a mouse model of gamma-herpesvirus pathogenesis. Curr. Opin. Microbiol. 2:403-409.
49. Stevenson, P. G., and P. C. Doherty. 1999. Non-antigen-specific B-cell activation following murine gammaherpesvirus infection is CD4 independent in vitro but CD4 dependent in vivo. J. Virol. 73:1075-1079.
50. Sunil-Chandra, N. P., S. Efstathiou, J. Arno, and A. A. Nash. 1992. Virological and pathological features of mice infected with murine gamma-herpesvirus 68. J. Gen. Virol. 73:2347-2356.
51. Sunil-Chandra, N. P., S. Efstathiou, and A. A. Nash. 1992. Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo. J. Gen. Virol. 73:3275-3279.
52. Symensma, T. L., D. Martinez-Guzman, Q. Jia, E. Bortz, T. T. Wu, N. Rudra-Ganguly, S. Cole, H. Herschman, and R. Sun. 2003. COX-2 induction during murine gammaherpesvirus 68 infection leads to enhancement of viral gene expression. J. Virol. 77:12753-12763.
53. Thorley-Lawson, D. A. 2001. Epstein-Barr virus: exploiting the immune system. Nat. Rev. Immunol. 1:75-82.
54. Thorley-Lawson, D. A., and G. J. Babcock. 1999. A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells. Life Sci. 65:1433-1453.
55. Thorley-Lawson, D. A., and K. P. Mann. 1985. Early events in Epstein-Barr virus infection provide a model for B cell activation. J. Exp. Med. 162:45-59.
56. Usherwood, E. J., A. J. Ross, D. J. Allen, and A. A. Nash. 1996. Murine gammaherpesvirus-induced splenomegaly: a critical role for CD4 T cells. J. Gen. Virol. 77:627-630.
57. Virgin, H. W., and S. H. Speck. 1999. Unraveling immunity to gammaherpesviruses: a new model for understanding the role of immunity in chronic virus infection. Curr. Opin. Immunol. 11:371-379.
58. Virgin, H. W., IV, P. Latreille, P. Wamsley, K. Hallsworth, K. E. Weck, A. J. Dal Canto, and S. H. Speck. 1997. Complete sequence and genomic analysis of murine gammaherpesvirus 68. J. Virol. 71:5894-5904.
59. Virgin, H. W., IV, R. M. Presti, X. Y. Li, C. Liu, and S. H. Speck. 1999. Three distinct regions of the murine gammaherpesvirus 68 genome are transcriptionally active in latently infected mice. J. Virol. 73:2321-2332.
60. Weck, K. E., M. L. Barkon, L. I. Yoo, S. H. Speck, and H. I. Virgin. 1996. Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68. J. Virol. 70:6775-6780.
61. Weck, K. E., S. S. Kim, H. W. Virgin IV, and S. H. Speck. 1999. B cells regulate murine gammaherpesvirus 68 latency. J. Virol. 73:4651-4661.
62. Weck, K. E., S. S. Kim, H. W. Virgin IV, and S. H. Speck. 1999. Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells. J. Virol. 73:3273-3283.
63. Willer, D. O., and S. H. Speck. 2003. Long-term latent murine gammaherpesvirus 68 infection is preferentially found within the surface immunoglobulin D-negative subset of splenic B cells in vivo. J. Virol. 77:8310-8321.
64. Zimber-Strobl, U., B. Kempkes, G. Marschall, R. Zeidler, C. Van Kooten, J. Banchereau, G. W. Bornkamm, and W. Hammerschmidt. 1996. Epstein-Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival. EMBO J. 15:7070-7078.