Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

Journal of Clinical Investigation

Volumn 124, Issue 5, 2014, Pages 1928-1944

  Malouli, Daniel ^a   Hansen, Scott G ^a   Nakayasu, Ernesto S ^b,d   Marshall, Emily E ^a   Hughes, Colette M ^a   Ventura, Abigail B ^a   Gilbride, Roxanne M ^a   Lewis, Matthew S ^a   Xu, Guangwu ^a   Kreklywich, Craig ^a   Whizin, Nathan ^a   Fischer, Miranda ^c   Legasse, Alfred W ^c   Viswanathan, Kasinath ^a,e   Siess, Don ^c   Camp II, David G ^b   Axthelm, Michael K ^c   Kahl, Christoph ^c   DeFilippis, Victor R ^a   Smith, Richard D ^b   Streblow, Daniel N ^a   Picker, Louis J ^a,c   Früh, Klaus ^a,c   more..

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b PACIFIC NORTHWEST NATIONAL LABORATORY   (United States)

^c OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^d PURDUE UNIVERSITY   (United States)

^e Advinus Therapeutics Private Limited Bangalore   (India)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOMEGALOVIRUS ANTIGEN PP65; CYTOMEGALOVIRUS VACCINE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; RHESUS CYTOMEGALOVIRUS DELTA PHOSPHOPROTEIN 65AB; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIGEN PRESENTATION; ARTICLE; CELL SPECIFICITY; CONTROLLED STUDY; CYTOMEGALOVIRUS INFECTION; FEMALE; GENE DOSAGE; IMMUNOMODULATION; IN VITRO STUDY; MALE; NONHUMAN; PERSISTENT INFECTION; PRIMARY INFECTION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN SECRETION; PROVOCATION TEST; RHESUS MONKEY; T LYMPHOCYTE; VIRION; VIROGENESIS; VIRUS IMMUNITY;

ANIMALS; ANTIGEN PRESENTATION; CELL LINE; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; CYTOMEGALOVIRUS VACCINES; GENE DELETION; HUMANS; MACACA MULATTA; MICE; PHOSPHOPROTEINS; T-LYMPHOCYTES; VIRAL MATRIX PROTEINS;

EID: 84899721223     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI67420     Document Type: Article

References (80)

1. Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202-213.
2. Boppana SB, Fowler KB, Britt WJ, Stagno S, Pass RF. Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus. Pediatrics. 1999; 104(1 pt 1):55-60.
3. Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med. 1992;326(10):663-667.
4. Fowler KB, Stagno S, Pass RF. Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA. 2003;289(8):1008-1011.
5. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am. 2011;25(1):151-169.
6. Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis. 2004;39(2):233-239.
7. Ross SA, Arora N, Novak Z, Fowler KB, Britt WJ, Boppana SB. Cytomegalovirus reinfections in healthy seroimmune women. J Infect Dis. 2010; 201(3):386-389.
8. Stratton KR, Durch JS, Lawrence RS. Vaccines For The 21St Century. Washington, DC, USA: National Academy Press; 2000.
9. Plotkin SA, Starr SE, Friedman HM, Gonczol E, Weibel RE. Protective effects of Towne cytomegalovirus vaccine against low-passage cytomegalovirus administered as a challenge. J Infect Dis. 1989; 159(5):860-865.
10. Plotkin SA, et al. Towne-vaccine-induced prevention of cytomegalovirus disease after renal transplants. Lancet. 1984;1(8376):528-530.
11. Bernstein DI. Vaccines for cytomegalovirus. Infect Disord Drug Targets. 2011;11(5):514-525.
12. Pass RF, et al. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med. 2009; 360(12):1191-1199.
13. Kharfan-Dabaja MA, et al. A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012;12(4):290-299.
14. Kern F, et al. Cytomegalovirus (CMV) phosphoprotein 65 makes a large contribution to shaping the T cell repertoire in CMV-exposed individuals. J Infect Dis. 2002;185(12):1709-1716.
15. Sylwester AW, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673-685.
16. McLaughlin-Taylor E, et al. Identification of the major late human cytomegalovirus matrix protein pp65 as a target antigen for CD8+ virus-specific cytotoxic T lymphocytes. J Med Virol. 1994; 43(1):103-110.
17. Wills MR, et al. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J Virol. 1996;70(11):7569-7579.
18. Varnum SM, et al. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J Virol. 2004;78(20):10960-10966.
19. Browne EP, Shenk T. Human cytomegalovirus UL83-coded pp65 virion protein inhibits antiviral gene expression in infected cells. Proc Natl Acad Sci U S A. 2003;100(20):11439-11444.
20. Abate DA, Watanabe S, Mocarski ES. Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response. J Virol. 2004; 78(20):10995-11006.
21. Cristea IM, et al. Human cytomegalovirus pUL83 stimulates activity of the viral immediate-early promoter through its interaction with the cellular IFI16 protein. J Virol. 2010;84(15):7803-7814.
22. Arnon TI, et al. Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. Nat Immunol. 2005;6(5):515-523.
23. Gilbert MJ, Riddell SR, Plachter B, Greenberg PD. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature. 1996;383(6602):720-722.
24. Odeberg J, Plachter B, Branden L, Soderberg-Naucler C. Human cytomegalovirus protein pp65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR alpha-chain. Blood. 2003;101(12):4870-4877.
25. Britt WJ, Auger D. Human cytomegalovirus virion-associated protein with kinase activity. J Virol. 1986;59(1):185-188.
26. Somogyi T, Michelson S, Masse MJ. Genomic location of a human cytomegalovirus protein with protein kinase activity (PK68). Virology. 1990; 174(1):276-285.
27. Yao ZQ, et al. Site-directed mutation in a conserved kinase domain of human cytomegalovirus-pp65 with preservation of cytotoxic T lymphocyte targeting. Vaccine. 2001;19(13-14):1628-1635.
28. Gallina A, et al. Polo-like kinase 1 as a target for human cytomegalovirus pp65 lower matrix protein. J Virol. 1999;73(2):1468-1478.
29. Kamil JP, Coen DM. Human cytomegalovirus protein kinase UL97 forms a complex with the tegument phosphoprotein pp65. J Virol. 2007; 81(19):10659-10668.
30. Schmolke S, Kern HF, Drescher P, Jahn G, Plachter B. The dominant phosphoprotein pp65 (UL83) of human cytomegalovirus is dispensable for growth in cell culture. J Virol. 1995;69(10):5959-5968.
31. Chevillotte M, et al. Major tegument protein pp65 of human cytomegalovirus is required for the incorporation of pUL69 and pUL97 into the virus particle and for viral growth in macrophages. J Virol. 2009;83(6):2480-2490.
32. Brune W, Hengel H, Koszinowski UH. A mouse model for cytomegalovirus infection. Curr Protoc Immunol. 2001;Chapter 19:Unit 19.7.
33. Schleiss MR. Animal models of congenital cytomegalovirus infection: an overview of progress in the characterization of guinea pig cytomegalovirus (GPCMV). J Clin Virol. 2002;25(suppl 2):S37-S49.
34. Powers C, Fruh K. Rhesus CMV: an emerging animal model for human CMV. Med Microbiol Immunol. 2008;197(2):109-115.
35. Yue Y, Barry PA. Rhesus cytomegalovirus a nonhuman primate model for the study of human cytomegalovirus. Adv Virus Res. 2008;72:207-226.
36. Hansen SG, Strelow LI, Franchi DC, Anders DG, Wong SW. Complete sequence and genomic analysis of rhesus cytomegalovirus. J Virol. 2003; 77(12):6620-6636.
37. Yue Y, Kaur A, Zhou SS, Barry PA. Characterization and immunological analysis of the rhesus cytomegalovirus homologue (Rh112) of the human cytomegalovirus UL83 lower matrix phosphoprotein (pp65). J Gen Virol. 2006;87(pt 4):777-787.
38. Malouli D, et al. Reevaluation of the coding potential and proteomic analysis of the BAC-derived rhesus cytomegalovirus strain 68-1. J Virol. 2012; 86(17):8959-8973.
39. Chang WL, Barry PA. Cloning of the full-length rhesus cytomegalovirus genome as an infectious and self-excisable bacterial artificial chromosome for analysis of viral pathogenesis. J Virol. 2003; 77(9):5073-5083.
40. Price DA, et al. Induction and evolution of cytomegalovirus-specific CD4+ T cell clonotypes in rhesus macaques. J Immunol. 2008;180(1):269-280.
41. Hansen SG, et al. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med. 2009;15(3):293-299.
42. Hansen SG, et al. Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus. Science. 2010; 328(5974):102-106.
43. Hel Z, et al. A novel chimeric Rev, Tat, and Nef (Retanef) antigen as a component of an SIV/HIV vaccine. Vaccine. 2002;20(25-26):3171-3186.
44. Abel K, et al. Vaccine-induced control of viral shedding following rhesus cytomegalovirus challenge in rhesus macaques. J Virol. 2011;85(6):2878-2890.
45. Yue Y, et al. Immunogenicity and protective efficacy of DNA vaccines expressing rhesus cytomegalovirus glycoprotein B, phosphoprotein 65-2, and viral interleukin-10 in rhesus macaques. J Virol. 2007; 81(3):1095-1109.
46. Yue Y, et al. Evaluation of recombinant modified vaccinia Ankara virus-based rhesus cytomegalovirus vaccines in rhesus macaques. Med Microbiol Immunol. 2008;197(2):117-123.
47. Mohr CA, et al. A spread-deficient cytomegalovirus for assessment of first-target cells in vaccination. J Virol. 2010;84(15):7730-7742.
48. Hansen SG, et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011;473(7348):523-527.
49. Kalejta RF. Tegument proteins of human cytomegalovirus. Microbiol Mol Biol Rev. 2008;72(2):249-265.
50. DeFilippis V, Fruh K. Rhesus cytomegalovirus particles prevent activation of interferon regulatory factor 3. J Virol. 2005;79(10):6419-6431.
51. Morello CS, Cranmer LD, Spector DH. In vivo replication, latency, and immunogenicity of murine cytomegalovirus mutants with deletions in the M83 and M84 genes, the putative homologs of human cytomegalovirus pp65 (UL83). J Virol. 1999; 73(9):7678-7693.
52. Cranmer LD, Clark CL, Morello CS, Farrell HE, Rawlinson WD, Spector DH. Identification, analysis, and evolutionary relationships of the putative murine cytomegalovirus homologs of the human cytomegalovirus UL82 (pp71) and UL83 (pp65) matrix phosphoproteins. J Virol. 1996;70(11):7929-7939.
53. McGregor A, Liu F, Schleiss MR. Molecular, biological, and in vivo characterization of the guinea pig cytomegalovirus (CMV) homologs of the human CMV matrix proteins pp71 (UL82) and pp65 (UL83). J Virol. 2004;78(18):9872-9889.
54. Voigt V, et al. Murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells. Proc Natl Acad Sci U S A. 2003; 100(23):13483-13488.
55. Bubic I, et al. Gain of virulence caused by loss of a gene in murine cytomegalovirus. J Virol. 2004; 78(14):7536-7544.
56. Oxford KL, et al. Protein coding content of the UL) b' region of wild-type rhesus cytomegalovirus. Virology. 2008;373(1):181-188.
57. Lilja AE, Shenk T. Efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types. Proc Natl Acad Sci U S A. 2008; 105(50):19950-19955.
58. Berencsi K, et al. A canarypox vector-expressing cytomegalovirus (CMV) phosphoprotein 65 induces long-lasting cytotoxic T cell responses in human CMV-seronegative subjects. J Infect Dis. 2001; 183(8):1171-1179.
59. Selinsky C, et al. A DNA-based vaccine for the prevention of human cytomegalovirus-associated diseases. Hum Vaccin. 2005;1(1):16-23.
60. Bernstein DI, et al. Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers. Vaccine. 2009;28(2):484-493.
61. Jacobson MA, et al. A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain). Vaccine. 2009;27(10):1540-1548.
62. La Rosa C, et al. Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant. J Infect Dis. 2012;205(8):1294-1304.
63. Feuchtinger T, et al. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116(20):4360-4367.
64. Peggs KS, et al. Directly selected cytomegalovirus- reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis. 2011;52(1):49-57.
65. Mackinnon S, Thomson K, Verfuerth S, Peggs K, Lowdell M. Adoptive cellular therapy for cytomegalovirus infection following allogeneic stem cell transplantation using virus-specific T cells. Blood Cells Mol Dis. 2008;40(1):63-67.
66. Micklethwaite K, et al. Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13(6):707-714.
67. Peggs KS, Mackinnon S. Clinical trials with CMV-specific T cells. Cytotherapy. 2002;4(1):21-28.
68. Schub A, Schuster IG, Hammerschmidt W, Moosmann A. CMV-specific TCR-transgenic T cells for immunotherapy. J Immunol. 2009;183(10):6819-6830.
69. Hansen SG, et al. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science. 2013;340(6135):1237874.
70. Barry PA, et al. Nonhuman primate models of intrauterine cytomegalovirus infection. ILAR J. 2006; 47(1):49-64.
71. Tarantal AF, Salamat MS, Britt WJ, Luciw PA, Hendrickx AG, Barry PA. Neuropathogenesis induced by rhesus cytomegalovirus in fetal rhesus monkeys (Macaca mulatta). J Infect Dis. 1998;177(2):446-450.
72. Chang WL, Kirchoff V, Pari GS, Barry PA. Replication of rhesus cytomegalovirus in life-expanded rhesus fibroblasts expressing human telomerase. J Virol Methods. 2002;104(2):135-146.
73. Zhang Y, Buchholz F, Muyrers JP, Stewart AF. A new logic for DNA engineering using recombination in Escherichia coli. Nat Genet. 1998;20(2):123-128.
74. Muyrers JP, Zhang Y, Testa G, Stewart AF. Rapid modification of bacterial artificial chromosomes by ET-recombination. Nucleic Acids Res. 1999; 27(6):1555-1557.
75. Lee EC, et al. A highly efficient Escherichia colibased chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics. 2001;73(1):56-65.
76. Cherepanov PP, Wackernagel W. Gene disruption in Escherichia coli: TcR and KmR cassettes with the option of Flp-catalyzed excision of the antibiotic-resistance determinant. Gene. 1995;158(1):9-14.
77. Livesay EA, et al. Fully automated four-column capillary LC-MS system for maximizing throughput in proteomic analyses. Anal Chem. 2008; 80(1):294-302.
78. Kim S, Gupta N, Pevzner PA. Spectral probabilities and generating functions of tandem mass spectra: a strike against decoy databases. J Proteome Res. 2008; 7(8):3354-3363.
79. Ishihama Y, et al. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol Cell Proteomics. 2005;4(9):1265-1272.
80. Cline AN, Bess JW, Piatak M, Piatak M Jr, Lifson JD. Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS. J Med Primatol. 2005; 34(5-6):303-312.