HCMV: molecular basis of persistence and latency

doi:10.1017/CBO9780511545313.043

42 - HCMV: molecular basis of persistence and latency

from Part III - Pathogenesis, clinical disease, host response, and epidemiology: HCMV

Published online by Cambridge University Press: 24 December 2009

Michael A. Jarvis and

Jay A. Nelson

Edited by

Ann Arvin ,

Gabriella Campadelli-Fiume ,

Richard Whitley and

Michael A. Jarvis: Affiliation:
Vaccine and Gene Therapy Institute, Oregon Health Science University, Portland, OR, USA
Jay A. Nelson: Affiliation:
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR, USA
Ann Arvin: Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume: Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski: Affiliation:
Emory University, Atlanta
Patrick S. Moore: Affiliation:
University of Pittsburgh
Bernard Roizman: Affiliation:
University of Chicago
Richard Whitley: Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi: Affiliation:
University of Osaka, Japan

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Summary

Introduction

Human cytomegalovirus (HCMV) is an ubiquitous β-herpesvirus that establishes a lifelong infection within the host. Although HCMV is generally asymptomatic within the normal individual, the virus causes severe and incapacitating disease in immune compromised patients (Pass, 2001). A critical component for HCMV persistence in the non-immune compromised host is the ability of the virus to establish cellular sites of latency as well as persistent infection. During latency, the HCMV genome is maintained within the cell with limited viral gene expression reactivating virus upon cellular stimulation. In HCMV persistent infection, infectious virus is continually produced in the cell with minimal cytopathic effect thereby enabling long-term infection. Endothelial cells (ECs) and specific subpopulations of the myeloid lineage are believed to represent important sites of persistent HCMV replication and latency, respectively. Recent studies of HCMV and the closely related murine cytomegalovirus (MCMV) are beginning to identify the virally encoded genetic determinants required for replication in these cell types. The establishment of latent infection in myeloid cells that are critical cellular components of the host immune system, also closely interconnects HCMV and the host immune response. This chapter will focus on the role of ECs and myeloid cells as sites of CMV persistent replication and latency, and the viral mechanisms that modulate cellular functions to ensure survival and reactivation within the host.

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Type: Chapter
Information: Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
, pp. 765 - 779

DOI: https://doi.org/10.1017/CBO9780511545313.043 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2007

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References

Adler, S. P., Chandrika, T., Lawrence, L., and Baggett, J. (1983). Cytomegalovirus infections in neonates acquired by blood transfusions. Pediatr. Infect. Dis., 2, 114–118.CrossRef Google Scholar PubMed

Adler, S. P., Baggett, J., and McVoy M. (1985). Transfusion-associated cytomegalovirus infections in seropositive cardiac surgery patients. Lancet, 2, 743–747.CrossRef Google Scholar PubMed

Allavena, P., Piemonti, L., Longoni, D., Bernasconi, S., Stoppacciaro, A., Ruco, L., and Mantovani, A. (1998). IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. Eur. J. Immunol., 28, 359–369.3.0.CO;2-4>CrossRef Google Scholar PubMed

Asadullah, K., Prosch, S., Audring, H.et al. (1999). A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: an association with systemic tumour necrosis factor alpha overexpression. Br. J. Dermatol., 141, 94–102.CrossRef Google Scholar PubMed

Bolovan-Fritts, C. and Wiedeman J. A. (2001). Human cytomegalovirus strain Toledo lacks a virus-encoded tropism factor required for infection of aortic endothelial cells. J. Infect. Dis., 184, 1252–1261.CrossRef Google Scholar PubMed

Bolovan-Fritts, C. A., Mocarski, E. S., and Wiedeman J. A. (1999). Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood, 93, 394–398.Google Scholar PubMed

Borst, E. M., Hahn, G., Koszinowski, U. H., and Messerle, M. (1999). Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J. Virol., 73, 8320–8329.Google Scholar PubMed

Bowden, R. A. (1995). Transfusion-transmitted cytomegalovirus infection. Hematol. Oncol. Clin. North Am., 9, 155–166.CrossRef Google Scholar PubMed

Bowden, R. A., Slichter, S. J., Sayers, M.et al. (1995). A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant. Blood, 86, 3598–3603.Google Scholar PubMed

Brune, W., Menard, C., Heesemann, J., and Koszinowski, U. H. (2001). A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism. Science, 291, 303–305.CrossRef Google Scholar PubMed

Brytting, M., Mousavi-Jazi, M., Bostrom, L.et al. (1995). Cytomegalovirus DNA in peripheral blood leukocytes and plasma from bone marrow transplant recipients. Transplantation, 60, 961–965.CrossRef Google Scholar PubMed

Burns, L. J., Pooley, J. C., Walsh, D. J., Vercellotti, G. M., Weber, M. L. and Kovacs, A. (1999). Intercellular adhesion molecule-1 expression in endothelial cells is activated by cytomegalovirus immediate early proteins. Transplantation, 67, 137–44.CrossRef Google Scholar PubMed

Cebulla, C. M., Miller, D. M., Knight, D. A., Briggs, B. R., McGaughy, V. and Sedmak, D. D. (2000). Cytomegalovirus induces sialyl Lewis(x) and Lewis(x) on human endothelial cells. Transplantation, 69, 1202–1209.CrossRef Google Scholar PubMed

Colberg-Poley, A. M., Patel, M. B., Erezo, D. P., and Slater, J. E. (2000). Human cytomegalovirus UL37 immediate-early regulatory proteins traffic through the secretory apparatus and to mitochondria. J. Gen. Virol., 81, 1779–1789.CrossRef Google Scholar

Dankner, W. M., McCutchan, J. A., Richman, D. D., Hirata, K., and Spector, S. A. (1990). Localization of human cytomegalovirus in peripheral blood leukocytes by in situ hybridization. J. Infect. Dis., 161, 31–36.CrossRef Google Scholar PubMed

Dargan, D. J., Jamieson, F. E., MacLean, J., Dolan, A., Addison, C., and McGeoch, D. J. (1997). The published DNA sequence of human cytomegalovirus strain AD169 lacks 929 base pairs affecting genes UL42 and UL43. J. Virol., 71, 9833–9836.Google Scholar PubMed

Docke, W. D., Prosch, S., Fietze, E.et al. (1994). Cytomegalovirus reactivation and tumour necrosis factor. Lancet, 343, 268–269.CrossRef Google Scholar PubMed

Einhorn, L. and Ost, A. (1984). Cytomegalovirus infection of human blood cells. J. Infect. Dis., 149, 207–214.CrossRef Google Scholar PubMed

Fietze, E., Prosch, S., Reinke, P. (1994). Cytomegalovirus infection in transplant recipients. The role of tumor necrosis factor. Transplantation, 58, 675–680.CrossRef Google Scholar PubMed

Fish, K. N., Söderberg-Naucler, C., Mills, L. K., Stenglein, S., and Nelson, J. A. (1998). Human cytomegalovirus persistently infects aortic endothelial cells. J. Virol., 72, 5661–5668.Google Scholar PubMed

Friedman, H. M., Macarak, E. J., MacGregor, R. R., Wolfe, J., and Kefalides, N. A. (1981). Virus infection of endothelial cells. J. Infect. Dis., 143, 266–273.CrossRef Google Scholar PubMed

Gerna, G., Percivalle, E., Lilleri, D.et al. (2005). Dendritic-cell infection by human cytomegalovirus is restricted to strains carrying functional UL131–128 genes and mediates efficient viral antigen presentation to CD8+ T cells. J. Gen. Virol., 86, 275–84.CrossRef Google Scholar PubMed

Girgis, R. E., Tu, I., Berry, G. J.et al. (1996). Risk factors for the development of obliterative bronchiolitis after lung transplantation. J. Heart Lung Transpl., 15, 1200–1208.Google Scholar PubMed

Gnann, J. W. Jr., Ahlmen, J., Svalander, C., Olding, L., Oldstone, M. B., and Nelson, J. A. (1988). Inflammatory cells in transplanted kidneys are infected by human cytomegalovirus. Am. J. Pathol., 132, 239–248.Google Scholar PubMed

Goldmacher, V. S. (2002). vMIA, a viral inhibitor of apoptosis targeting mitochondria. Biochimie, 84, 177–185.CrossRef Google Scholar PubMed

Goldmacher, V. S., Bartle, L. M., Skaletskaya, A.et al. (1999). A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2. Proc. Natl Acad. Sci. USA, 96, 12536–12541.CrossRef Google Scholar

Goodrum, F. D., Jordan, C. T., High, K., and Shenk, T. (2002). Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: a model for latency. Proc. Natl. Acad. Sci. USA, 99, 16255–16260.CrossRef Google Scholar PubMed

Grattan, M. T., Moreno-Cabral, C. E., Starnes, V. A., Oyer, P. E.Stinson, E. B., and Shumway, N. E. (1989). Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. J. Am. Med. Assoc., 261, 3561–3566.CrossRef Google Scholar PubMed

Greaves, R. F. and Mocarski, E. S. (1998). Defective growth correlates with reduced accumulation of a viral DNA replication protein after low-multiplicity infection by a human cytomegalovirus ie1 mutant. J. Virol., 72, 366–379.Google Scholar PubMed

Grundy, J. E., Lawson, K. M., MacCormac, L. P., Fletcher, J. M., and Yong, K. L. (1998). Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C–X–C chemokines and transmit virus by direct neutrophil– endothelial cell contact and during neutrophil transendothelial migration. J. Infect. Dis., 177, 1465–1474.CrossRef Google Scholar PubMed

Gyorkey, F., Melnick, J. L., Guinn, G. A., Gyorkey, P., and DeBakey, M. E. (1984). Herpesviridae in the endothelial and smooth muscle cells of the proximal aorta in arteriosclerotic patients. Exp. Mol. Pathol., 40, 328–339.CrossRef Google Scholar PubMed

Hahn, G., Jores, R., and Mocarski, E. S. (1998). Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc. Natl Acad. Sci. USA, 95, 3937–3942.CrossRef Google Scholar

Hahn, G., Khan, H., Baldanti, F., Koszinowski, U. H., Revello, M. G. and Gerna, G. (2002). The human cytomegalovirus ribonucleotide reductase homolog UL45 is dispensable for growth in endothelial cells, as determined by a BAC-cloned clinical isolate of human cytomegalovirus with preserved wild-type characteristics. J. Virol., 76, 9551–9555.CrossRef Google Scholar PubMed

Hahn, G., Rose, D., Wagner, M., Rhiel, S., and McVoy, M. A. (2003). Cloning of the genomes of human cytomegalovirus strains Toledo, TownevarRIT3, and Towne long as BACs and site-directed mutagenesis using a PCR-based technique. Virology, 307, 164–177.CrossRef Google Scholar

Hahn, G., Revello, M. G., Patrone, M.et al. (2004). Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J. Virol. 78, 10023–10033.CrossRef Google Scholar PubMed

Hanson, L. K., Dalton, B. L., and Karabekian, Z. (1999a). Transcriptional analysis of the murine cytomegalovirus HindIII-I region: identification of a novel immediate-early gene region. Virology, 260, 156–164.CrossRef Google Scholar

Hanson, L. K., Slater, J. S., Karabekian, Z.et al. (1999b). Replication of murine cytomegalovirus in differentiated macrophages as a determinant of viral pathogenesis. J. Virol., 73, 5970–5980.Google Scholar

Hanson, L. K., Slater, J. S., Karabekian, Z., Ciocco-Schmitt, G. and Campbell, A. E. (2001). Products of US22 genes M140 and M141 confer efficient replication of murine cytomegalovirus in macrophages and spleen. J. Virol., 75, 6292–6302.CrossRef Google Scholar PubMed

Harada, A., Sekido, N., Akahoshi, T., Wada, T., Mukaida, N., and Matsushima, K. (1994). Essential involvement of interleukin-8 (IL-8) in acute inflammation. J. Leukoc. Biol., 56, 559–564.CrossRef Google Scholar

Hatch, W. C., Freedman, A. R., Boldthoule, D. M., Groopman, J. E., and Terwilliger, E. F. (1997). Differential effects of interleukin-13 on cytomegalovirus and human immunodeficiency virus infection in human alveolar macrophages. Blood, 89, 3443–3450.Google Scholar PubMed

Hendrix, M., Dormans, P. H. J., Kitseelar, P., Bosman, F., and Bruggeman, C. A. (1989). The presence of CMV nucleic acids arterial walls of atherosclerotic and non-atherosclerotic patients. Am. J. Path., 134, 1151–1157.Google Scholar

Hendrix, M. G., Salimans, M. M. van Boven, C. P., and Bruggeman, C. A. (1990). High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. Am. J. Pathol., 136, 23–28.Google Scholar

Hersman, J., Meyers, J. D., Thomas, E. D., Buckner, C. D., and Clift, R. (1982). The effect of granulocyte transfusions on the incidence of cytomegalovirus infection after allogeneic marrow transplantation. Ann. Intern. Med., 96, 149–152.CrossRef Google Scholar PubMed

Ho, M. (1990). Epidemiology of cytomegalovirus infections. Rev. Infect. Dis., 12 (Suppl. 7), S701–5710.CrossRef Google Scholar PubMed

Hobom, U., Brune, W., Messerle, M., Hahn, G., and Koszinowski, U. H. (2000). Fast screening procedures for random transposon libraries of cloned herpesvirus genomes: mutational analysis of human cytomegalovirus envelope glycoprotein genes. J. Virol., 74, 7720–7729.CrossRef Google Scholar PubMed

Howell, C. L., Miller, M. J., and Martin, W. J. (1979). Comparison of rates of virus isolation from leukocyte populations separated from blood by conventional and Ficoll-Paque/Macrodex methods. J. Clin. Microbiol., 10, 533–537.Google Scholar PubMed

Humar, A., Gillingham, K. J., Payne, W. D., Dunn, D. L., Sutherland, D. E., and Matas, A. J. (1999a). Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients. Transplantation, 68, 1879–1883.CrossRef Google Scholar

Humar, A., Louis, St P., Mazzulli, T.et al. (1999b). Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplant recipients. J. Infect. Dis., 179, 484–488.CrossRef Google Scholar

Hummel, M., Zhang, Z., Yan, S. (2001). Allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: a model for reactivation from latency. J. Virol., 75, 4814–4822.CrossRef Google Scholar PubMed

Ibanez, C. E., Schrier, R., Ghazal, P., Wiley, C., and Nelson, J. A. (1991). Human cytomegalovirus productively infects primary differentiated macrophages. J. Virol., 65, 6581–6588.Google Scholar PubMed

Joo, F. (1992). The cerebral microvessels in culture, an update. J. Neurochem., 58, 1–17.CrossRef Google Scholar

Kahl, M., Siegel-Axel D., Stenglein S., Jahn, G., and Sinzger, C. (2000). Efficient lytic infection of human arterial endothelial cells by human cytomegalovirus strains. J. Virol., 74, 7628–7635.CrossRef Google Scholar PubMed

Keenan, R. J., Lega, M. E., Dummer, J. S.et al. (1991). Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation. Transplantation, 51, 433–438.CrossRef Google Scholar PubMed

Knight, D. A., Waldman, W. J., and Sedmak, D. D. (1999). Cytomegalovirus-mediated modulation of adhesion molecule expression by human arterial and microvascular endothelial cells. Transplantation, 68, 1814–1818.CrossRef Google Scholar PubMed

Koffron, A., Varghese, T., and Hummel, M. (1999). Immunosuppression is not required for reactivation of latent murine cytomegalovirus. Transpl. Proc., 31, 1395–1396.CrossRef Google Scholar

Kondo, K., Kaneshima, H., and Mocarski, E. S. (1994). Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. Proc. Natl Acad. Sci. U S A, 91, 11879–11883.CrossRef Google Scholar PubMed

Kondo, K., Xu, J., and Mocarski, E. S. (1996). Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc. Natl Acad. Sci. USA, 93, 11137–11142.CrossRef Google Scholar PubMed

Koskinen, P., Lemstrom, K., Mattila, S., Hayry, P., and Nieminen, M. S. (1996). Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft. Clin. Transpl., 10, 487–493.Google Scholar PubMed

Kotenko, S. V., Saccani, S., Izotova, L. S., Mirochnitchenko, O. V., and Pestka, S. (2000). Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc. Natl Acad. Sci. USA, 97, 1695–1700.CrossRef Google Scholar

MacCormac, L. P. and Grundy, J. E. (1999). Two clinical isolates and the Toledo strain of cytomegalovirus contain endothelial cell tropic variants that are not present in the AD169, Towne, or Davis strains. J. Med. Virol., 57, 298–307.3.0.CO;2-P>CrossRef Google Scholar

Maciejewski, J. P., Bruening, E. E., Donahue, R. E., Mocarski, E. S., Young, N. S., and Jeor, St S. C. (1992). Infection of hematopoietic progenitor cells by human cytomegalovirus. Blood, 80, 170–178.Google Scholar PubMed

Maciejewski, J. P., Bruening, E. E., Donahue, R. E.et al. (1993). Infection of mononucleated phagocytes with human cytomegalovirus. Virology, 195, 327–336.CrossRef Google Scholar PubMed

Marchini, A., Liu, H., and Zhu, H. (2001). Human cytomegalovirus with IE-2 (UL122) deleted fails to express early lytic genes. J. Virol., 75, 1870–1878.CrossRef Google Scholar PubMed

Menard, C., Wagner, M., and Ruzsics, Z. (2003). Role of murine cytomegalovirus US22 gene family members in replication in macrophages. J. Virol., 77, 5557–5570.CrossRef Google Scholar PubMed

Mendelson, M., Monard, S., Sissons, P., and Sinclair, J. (1996). Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J. Gen. Virol., 77, 3099–3102.CrossRef Google Scholar PubMed

Minton, E. J., Tysoe, C., Sinclair, J. H., and Sissons, J. G. (1994). Human cytomegalovirus infection of the monocyte/macrophage lineage in bone marrow. J. Virol., 68, 4017–4021.Google Scholar PubMed

Mocarski, E. S., Prichard, M. N., Tan, C. S., and Brown, J. M. (1997). Reassessing the organization of the UL42–UL43 region of the human cytomegalovirus strain AD169 genome. Virology, 239, 169–175.CrossRef Google Scholar PubMed

Moses, A. V. and Nelson, J. A. (1994). HIV infection of human brain capillary endothelial cells – implications for AIDS dementia. Adv. Neuroimmunol., 4, 239–247.CrossRef Google Scholar PubMed

Movassagh, M., Gozlan, J., Senechal, B., Baillou, C., Petit, J. C., and Lemoine, F. M. (1996). Direct infection of CD34+ progenitor cells by human cytomegalovirus: evidence for inhibition of hematopoiesis and viral replication. Blood, 88, 1277–1283.Google Scholar PubMed

Murayama, T., Mukaida, N., Khabar, K. S., and Matsushima, K. (1998). Potential involvement of IL-8 in the pathogenesis of human cytomegalovirus infection. J. Leukoc. Biol., 64, 62–67.CrossRef Google Scholar PubMed

Myerson, D., Hackman, R. C., Nelson, J. A., Ward, D. C., and McDougall, J. K. (1984). Widespread presence of histologically occult cytomegalovirus. Hum. Pathol., 15, 430–439.CrossRef Google Scholar PubMed

Nordoy, I., Muller, F., Nordal, K. P.et al. (1999). Immunologic parameters as predictive factors of cytomegalovirus disease in renal allograft recipients. J. Infect. Dis., 180, 195–198.CrossRef Google Scholar PubMed

Nordoy, I., Muller, F., Nordal, K. P., Rollag, H., Aukrust, P., and Froland, S. S. (2000a). Chemokines and soluble adhesion molecules in renal transplant recipients with cytomegalovirus infection. Clin. Exp. Immunol., 120, 333–337.CrossRef Google Scholar

Nordoy, I., Muller, F., Nordal, K. P.et al. (2000b). The role of the tumor necrosis factor system and interleukin-10 during cytomegalovirus infection in renal transplant recipients. J. Infect. Dis., 181, 51–57.CrossRef Google Scholar

Oswald, I. P., Wynn, T. A., Sher, A., and James, S. L. (1992). Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation. Proc. Natl Acad. Sci. USA, 89, 8676–8680.CrossRef Google Scholar PubMed

Page, C., Rose, M., Yacoub, M., and Pigott, R. (1992). Antigenic heterogeneity of vascular endothelium. Am. J. Pathol., 141, 673–683.Google Scholar PubMed

Pampou, S., Gnedoy, S. N., Bystrevskaya, V. B.et al. (2000). Cytomegalovirus genome and the immediate-early antigen in cells of different layers of human aorta. Virchows Arch., 436, 539–552.CrossRef Google Scholar PubMed

Pass, R. F. (2001). Cytomegalovirus. In Knipe, D. M., Griffin, D. E., Lamb, R. A., Martin, M. A., Roizman, B., and Straus, S. E. (eds.), Fields Virology, 4th edn. pp. 2675–2705 Philadelphia: Lippincott Williams & Wilkins.Google Scholar

Patrone, M., Secchi, M., Fiorina, L., Ierardi, M., Milanesi, G., and Gallina, A. (2005). Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. J. Virol., 79, 8361–8373.CrossRef Google Scholar PubMed

Patterson, C. E. and Shenk, T. (1999). Human cytomegalovirus UL36 protein is dispensable for viral replication in cultured cells. J. Virol., 73, 7126–7131.Google Scholar PubMed

Petrie, B. L., Melnick, J. L., Adam, E., Burek, J., McCollum, C. H., and DeBakey, M. E. (1987). Nucleic acid sequences of human cytomegalovirus in cells cultured from human arterial tissue. J. Infect. Dis., 155, 158–159.CrossRef Google Scholar PubMed

Prösch, S., Staak, K., Stein, J.et al. (1995). Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by TNFalpha is mediated via induction of NF-kappaB. Virology, 208, 197–206.Google Scholar

Prösch, S., Heine, A. K., Volk, H. D., and Kruger, D. H. (2001). CCAAT/enhancer-binding proteins alpha and beta negatively influence the capacity of tumor necrosis factor alpha to up-regulate the human cytomegalovirus IE1/2 enhancer/promoter by nuclear factor kappa B during monocyte differentiation. J. Biol. Chem., 276, 40712–40720.Google Scholar

Rajotte, D., Arap, W., Hagedorn, M., Koivunen, E., Pasqualini, R., and Ruoslahti, E. (1998). Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. J. Clin. Invest., 102, 430–437.CrossRef Google Scholar PubMed

Reboredo, M., Greaves, R. F., and Hahn, G. (2004). Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication. J. Gen. Virol., 85, 3555–35567.CrossRef Google Scholar PubMed

Rice, G. P., Schrier, R. D., and Oldstone, M. B. (1984). Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. Proc. Natl Acad. Sci. USA, 81, 6134–6138.CrossRef Google Scholar PubMed

Ritter, T., Brandt, C., Prosch, S.et al. (2000). Stimulatory and inhibitory action of cytokines on the regulation of hCMV-IE promoter activity in human endothelial cells. Cytokine, 12, 1163–1170.CrossRef Google Scholar PubMed

Rue, C. A., Jarvis, M. A., Knoche, A. J.et al. (2004). A cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism. J. Virol., 78, 12529–12536.CrossRef Google Scholar PubMed

Schrier, R. D., Nelson, J. A., and Oldstone, M. B. (1985). Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science, 230, 1048–1051.CrossRef Google Scholar

Simmons, P., Kaushansky, K., and Torok-Storb, B. (1990). Mechanisms of cytomegalovirus-mediated myelosuppression: perturbation of stromal cell function versus direct infection of myeloid cells. Proc. Natl Acad. Sci. USA, 87, 1386–1390.CrossRef Google Scholar PubMed

Sindre, H., Tjonnfjord, G. E., Rollag, H.et al. (1996). Human cytomegalovirus suppression of and latency in early hematopoietic progenitor cells. Blood, 88, 4526–4533.Google Scholar PubMed

Sinzger, C., Grefte, A., Plachter, B., Gouw, A. S., The, T. H., and Jahn, G. (1995). Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J. Gen. Virol., 76, 741–750.CrossRef Google Scholar PubMed

Sinzger, C., Schmidt, K., Knapp, J.et al. (1999). Modification of human cytomegalovirus tropism through propagation in vitro is associated with changes in the viral genome. J. Gen. Virol., 80, 2867–2877.CrossRef Google Scholar PubMed

Sinzger, C., Kahl, M., Laib, K.et al. (2000). Tropism of human cytomegalovirus for endothelial cells is determined by a post-entry step dependent on efficient translocation to the nucleus. J. Gen. Virol., 81(Pt 12), 3021–3035.CrossRef Google Scholar PubMed

Skaletskaya, A., Bartle, L. M., Chittenden, T., McCormick, A. L., Mocarski, E. S., and Goldmacher, V. S. (2001). A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc. Natl Acad. Sci. USA, 98, 7829–7834.CrossRef Google Scholar PubMed

Slobbe-van Drunen, M. E., Hendrickx, A. T., Vossen, R. C., Speel, E. J., Dam-Mieras, M. C., and Bruggeman, C. A. (1998). Nuclear import as a barrier to infection of human umbilical vein endothelial cells by human cytomegalovirus strain AD169. Virus Res., 56, 149–156.CrossRef Google Scholar PubMed

Slobedman, B. and Mocarski, E. S. (1999). Quantitative analysis of latent human cytomegalovirus. J. Virol., 73, 4806–4812.Google Scholar PubMed

Smiley, M. L., Mar, E. C., and Huang, E. S. (1988). Cytomegalovirus infection and viral-induced transformation of human endothelial cells. J. Med. Virol., 25, 213–226.CrossRef Google Scholar PubMed

Smith, J. A. and Pari, G. S. (1995). Expression of human cytomegalovirus UL36 and UL37 genes is required for viral DNA replication. J. Virol., 69, 1925–1931.Google Scholar

Smith, M. A., Sundaresan, S., Mohanakumar, T.et al. (1998). Effect of development of antibodies to HLA and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome. J. Thorac. Cardiovasc. Surg., 116, 812–820.CrossRef Google Scholar PubMed

Söderberg, C., Larsson, S., Bergstedt-Lindqvist, S., and Moller, E. (1993). Definition of a subset of human peripheral blood mononuclear cells that are permissive to human cytomegalovirus infection. J. Virol., 67, 3166–3175.Google Scholar PubMed

Söderberg-Naucler, C., Fish, K. N., and Nelson, J. A. (1997a). Interferon-gamma and tumor necrosis factor-alpha specifically induce formation of cytomegalovirus-permissive monocyte-derived macrophages that are refractory to the antiviral activity of these cytokines. J. Clin. Invest., 100, 3154–3163.CrossRef Google Scholar

Söderberg-Naucler, C., Fish, K. N., and Nelson, J. A. (1997b). Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell, 91, 119–126.CrossRef Google Scholar

Söderberg-Naucler, C., Streblow, D. N., Fish, K. N., Allan-Yorke, J., Smith, P. P., and Nelson, J. A. (2001). Reactivation of latent human cytomegalovirus in CD14(+) monocytes is differentiation dependent. J. Virol., 75, 7543–7554.CrossRef Google Scholar PubMed

Speir, E., Modali, R., Huang, E. S., Leon, M. B., Shawl, F., Finkel, T., and Epstein, S. E. (1994). Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science, 265, 391–394.CrossRef Google Scholar PubMed

Spencer, J. V., Lockridge, K. M., Barry, P. A.et al. (2002). Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10. J. Virol., 76, 1285–1292.CrossRef Google Scholar PubMed

Stein, J., Volk, H. D., Liebenthal, C., Kruger, D. H., and Prosch, S. (1993). Tumour necrosis factor alpha stimulates the activity of the human cytomegalovirus major immediate early enhancer/promoter in immature monocytic cells. J. Gen. Virol., 74, 2333–2338.CrossRef Google Scholar PubMed

Taylor-Wiedeman, J., Sissons, J. G., Borysiewicz, L. K., and Sinclair, J. H. (1991). Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J. Gen. Virol., 72, 2059–2064.CrossRef Google Scholar PubMed

Taylor-Wiedeman, J., Hayhurst, G. P., Sissons, J. G., and Sinclair, J. H. (1993). Polymorphonuclear cells are not sites of persistence of human cytomegalovirus in healthy individuals. J. Gen. Virol., 74, 265–268.CrossRef Google Scholar

Taylor-Wiedeman, J., Sissons, P., and Sinclair, J. (1994). Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J. Virol., 68, 1597–1604.Google Scholar PubMed

Tegtmeier, G. E. (1989). Posttransfusion cytomegalovirus infections. Arch. Pathol. Lab. Med., 113, 236–245.Google Scholar PubMed

Tegtmeier, G. E. (1986). Transfusion-transmitted cytomegalovirus infections: significance and control. Vox Sang., 51(Suppl 1), 22–30.CrossRef Google Scholar PubMed

Tolkoff-Rubin, N. E. and Rubin, R. H. (1994). The interaction of immunosuppression with infection in the organ transplant recipient. Transpl. Proc., 26, 16–19.Google Scholar PubMed

Torok-Storb, B., Simmons, P., Khaira, D., Stachel, D., and Myerson, D. (1992). Cytomegalovirus and marrow function. Ann. Hematol., 64(Suppl), A128–A131.CrossRef Google Scholar PubMed

Turner, R. R., Beckstead, J. H., Warnke, R. A., and Wood, G. S. (1987). Endothelial cell phenotypic diversity. In situ demonstration of immunologic and enzymatic heterogeneity that correlates with specific morphologic subtypes. Am. J. Clin. Pathol., 87, 569–575.CrossRef Google Scholar PubMed

von Laer, D., Meyer-Koenig, U., Serr, A.et al. (1995a). Detection of cytomegalovirus DNA in CD34+ cells from blood and bone marrow. Blood, 86, 4086–4090.Google Scholar

von Laer, D., Serr, A., Meyer-Konig, U., Kirste, G., Hufert, F. T., and Haller, O. (1995b). Human cytomegalovirus immediate early and late transcripts are expressed in all major leukocyte populations in vivo [see comments]. J. Infect. Dis., 172, 365–370.CrossRef Google Scholar

Wagner, M., Ruzsics, Z., and Koszinowski, U. H. (2002). Herpesvirus genetics has come of age. Trends Microbiol., 10, 318–324.CrossRef Google Scholar PubMed

Waldman, W. J. and Knight, D. A. (1996). Cytokine-mediated induction of endothelial adhesion molecule and histocompatibility leukocyte antigen expression by cytomegalovirus-activated T cells. Am. J. Pathol., 148, 105–119.Google Scholar PubMed

Waldman, W. J., Knight, D. A., Huang, E. H., and Sedmak, D. D. (1995). Bidirectional transmission of infectious cytomegalovirus between monocytes and vascular endothelial cells: an in vitro model. J. Infect. Dis., 171, 263–272.CrossRef Google Scholar

Wang, D. and Shenk, T. (2005a). Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism. J. Virol., 79, 10330–10338.CrossRef Google Scholar

Wang, D. and Shenk, T. (2005b). Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc. Natl. Acad. Sci. USA, 102, 18153–18158.CrossRef Google Scholar

White, K. L., Slobedman, B., and Mocarski, E. S. (2000). Human cytomegalovirus latency-associated protein pORF94 is dispensable for productive and latent infection. J. Virol., 74, 9333–9337.CrossRef Google Scholar PubMed

Wiley, C. A. and Nelson, J. A. (1988). Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis. Am. J. Pathol., 133, 73–81.Google Scholar PubMed

Yamashiroya, H. M., Ghosh, L., Yang, R., and Robertson, A. L. (1988). Herpesviredae in the coronary arteries and aorta of young trauma victims. Am. J. Path., 130, 71–79.Google Scholar PubMed

Yu, D., Smith, G. A., Enquist, L. W., and Shenk, T. (2002). Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene. J. Virol., 76, 2316–2328.CrossRef Google Scholar PubMed

Zhang, H., Fu, S., Busch, A., Chen, F., Qin, L., and Bromberg, J. S. (2001). Identification of TNF-alpha-sensitive sites in HCMVie1 promoter. Exp. Mol. Pathol., 71, 106–114.CrossRef Google Scholar PubMed

Zhu, H., Shen Y., and Shenk T. (1995). Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J. Virol., 69, 7960–7970.Google Scholar PubMed

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