This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Staskus, K. A.
Right arrow Articles by Haase, A. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Staskus, K. A.
Right arrow Articles by Haase, A. T.

 Previous Article  |  Next Article 

Journal of Virology, May 1999, p. 4181-4187, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cellular Tropism and Viral Interleukin-6 Expression Distinguish Human Herpesvirus 8 Involvement in Kaposi's Sarcoma, Primary Effusion Lymphoma, and Multicentric Castleman's Disease

Katherine A. Staskus,1,* Ren Sun,2 George Miller,3,4,5 Paul Racz,6 Anthony Jaslowski,7 Craig Metroka,8 Helena Brett-Smith,9 and Ashley T. Haase1

Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 554551; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 900952; Departments of Molecular Biophysics and Biochemistry,3 Pediatrics,4 and Epidemiology and Public Health,5 Yale University School of Medicine, New Haven, Connecticut 06520; Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany6; David Grant Medical Center, Travis AFB, California 945357; Columbia University College of Physicians and Surgeons, New York, New York 100198; and Hospital of Saint Raphael, New Haven, Connecticut 065119

Received 23 September 1998/Accepted 15 February 1999

Human herpesvirus 8 (HHV-8) infection has been implicated in the etiology of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), three diseases that frequently develop in immunocompromised, human immunodeficiency virus-positive individuals. One hypothesis that would account for different pathological manifestations of infection by the same virus is that viral genes are differentially expressed in heterogeneous cell types. To test this hypothesis, we analyzed the localization and levels of expression of two viral genes expressed in latent and lytic infections and the viral homologue of interleukin-6 (vIL-6). We show that PEL parallels KS in the pattern of latent and lytic cycle viral gene expression but that the predominant infected cell type is a B cell. We also show that MCD differs from KS not only in the infected cell type (B-cell and T-cell lineage) but also in the pattern of viral gene expression. Only a few cells in the lesion are infected and all of these cells express lytic-cycle genes. Of possibly greater significance is the fact that in a comparison of KS, PEL, and MCD, we found dramatic differences in the levels of expression of vIL-6. Interleukin-6 is a B-cell growth and differentiation factor whose altered expression has been linked to plasma cell abnormalities, as well as myeloid and lymphoid malignancies. Our findings support the hypothesis that HHV-8 plays an important role in the pathogenesis of PEL and MCD, in which vIL-6 acts as an autocrine or paracrine factor in the lymphoproliferative processes common to both.

* Corresponding author. Mailing address: Department of Microbiology, University of Minnesota, UMHC196, 420 Delaware St., S.E., Minneapolis, MN 55455. Phone: (612) 624-9118. Fax: (612) 626-0623. E-mail: kathryn{at}lenti.med.umn.edu.

Journal of Virology, May 1999, p. 4181-4187, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chen, D., Sandford, G., Nicholas, J. (2009). Intracellular Signaling Mechanisms and Activities of Human Herpesvirus 8 Interleukin-6. J. Virol. 83: 722-733 [Abstract] [Full Text]  
  • Orzechowska, B. U., Powers, M. F., Sprague, J., Li, H., Yen, B., Searles, R. P., Axthelm, M. K., Wong, S. W. (2008). Rhesus macaque rhadinovirus-associated non-Hodgkin lymphoma: animal model for KSHV-associated malignancies. Blood 112: 4227-4234 [Abstract] [Full Text]  
  • Rappocciolo, G., Hensler, H. R., Jais, M., Reinhart, T. A., Pegu, A., Jenkins, F. J., Rinaldo, C. R. (2008). Human Herpesvirus 8 Infects and Replicates in Primary Cultures of Activated B Lymphocytes through DC-SIGN. J. Virol. 82: 4793-4806 [Abstract] [Full Text]  
  • Majerciak, V., Yamanegi, K., Allemand, E., Kruhlak, M., Krainer, A. R., Zheng, Z.-M. (2008). Kaposi's Sarcoma-Associated Herpesvirus ORF57 Functions as a Viral Splicing Factor and Promotes Expression of Intron-Containing Viral Lytic Genes in Spliceosome-Mediated RNA Splicing. J. Virol. 82: 2792-2801 [Abstract] [Full Text]  
  • Zhang, Y.-J., Bonaparte, R. S., Patel, D., Stein, D. A., Iversen, P. L. (2008). Blockade of viral interleukin-6 expression of Kaposi's sarcoma-associated herpesvirus. Molecular Cancer Therapeutics 7: 712-720 [Abstract] [Full Text]  
  • Guihot, A., Oksenhendler, E., Galicier, L., Marcelin, A.-G., Papagno, L., Bedin, A.-S., Agbalika, F., Dupin, N., Cadranel, J., Autran, B., Carcelain, G. (2008). Multicentric Castleman disease is associated with polyfunctional effector memory HHV-8-specific CD8+ T cells. Blood 111: 1387-1395 [Abstract] [Full Text]  
  • Davis, D. A., Singer, K. E., Reynolds, I. P., Haque, M., Yarchoan, R. (2007). Hypoxia Enhances the Phosphorylation and Cytotoxicity of Ganciclovir and Zidovudine in Kaposi's Sarcoma-Associated Herpesvirus Infected Cells. Cancer Res. 67: 7003-7010 [Abstract] [Full Text]  
  • Xu, Y., Ganem, D. (2007). Induction of chemokine production by latent Kaposi's sarcoma-associated herpesvirus infection of endothelial cells. J. Gen. Virol. 88: 46-50 [Abstract] [Full Text]  
  • Majerciak, V., Yamanegi, K., Nie, S. H., Zheng, Z.-M. (2006). Structural and Functional Analyses of Kaposi Sarcoma-associated Herpesvirus ORF57 Nuclear Localization Signals in Living Cells. J. Biol. Chem. 281: 28365-28378 [Abstract] [Full Text]  
  • Kovaleva, M., Bussmeyer, I., Rabe, B., Grotzinger, J., Sudarman, E., Eichler, J., Conrad, U., Rose-John, S., Scheller, J. (2006). Abrogation of Viral Interleukin-6 (vIL-6)-Induced Signaling by Intracellular Retention and Neutralization of vIL-6 with an Anti-vIL-6 Single-Chain Antibody Selected by Phage Display.. J. Virol. 80: 8510-8520 [Abstract] [Full Text]  
  • Rezaee, S. A. R., Cunningham, C., Davison, A. J., Blackbourn, D. J. (2006). Kaposi's sarcoma-associated herpesvirus immune modulation: an overview. J. Gen. Virol. 87: 1781-1804 [Abstract] [Full Text]  
  • Hong, G. K., Gulley, M. L., Feng, W.-H., Delecluse, H.-J., Holley-Guthrie, E., Kenney, S. C. (2005). Epstein-Barr Virus Lytic Infection Contributes to Lymphoproliferative Disease in a SCID Mouse Model. J. Virol. 79: 13993-14003 [Abstract] [Full Text]  
  • Yamanegi, K., Tang, S., Zheng, Z.-M. (2005). Kaposi's Sarcoma-Associated Herpesvirus K8{beta} Is Derived from a Spliced Intermediate of K8 Pre-mRNA and Antagonizes K8{alpha} (K-bZIP) To Induce p21 and p53 and Blocks K8{alpha}-CDK2 Interaction. J. Virol. 79: 14207-14221 [Abstract] [Full Text]  
  • Guihot, A., Couderc, L-J., Agbalika, F., Galicier, L., Bossi, P., Rivaud, E., Scherrer, A., Zucman, D., Katlama, C., Oksenhendler, E. (2005). Pulmonary manifestations of multicentric Castleman's disease in HIV infection: a clinical, biological and radiological study. Eur Respir J 26: 118-125 [Abstract] [Full Text]  
  • Meads, M. B., Medveczky, P. G. (2004). Kaposi's Sarcoma-associated Herpesvirus-encoded Viral Interleukin-6 Is Secreted and Modified Differently Than Human Interleukin-6: EVIDENCE FOR A UNIQUE AUTOCRINE SIGNALING MECHANISM. J. Biol. Chem. 279: 51793-51803 [Abstract] [Full Text]  
  • Deng, J.-H., Zhang, Y.-J., Wang, X.-P., Gao, S.-J. (2004). Lytic Replication-Defective Kaposi's Sarcoma-Associated Herpesvirus: Potential Role in Infection and Malignant Transformation. J. Virol. 78: 11108-11120 [Abstract] [Full Text]  
  • McAllister, S. C., Hansen, S. G., Ruhl, R. A., Raggo, C. M., DeFilippis, V. R., Greenspan, D., Fruh, K., Moses, A. V. (2004). Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells. Blood 103: 3465-3473 [Abstract] [Full Text]  
  • Casper, C., Nichols, W. G., Huang, M.-L., Corey, L., Wald, A. (2004). Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment. Blood 103: 1632-1634 [Abstract] [Full Text]  
  • Naranatt, P. P., Krishnan, H. H., Svojanovsky, S. R., Bloomer, C., Mathur, S., Chandran, B. (2004). Host Gene Induction and Transcriptional Reprogramming in Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8)-Infected Endothelial, Fibroblast, and B Cells: Insights into Modulation Events Early during Infection. Cancer Res. 64: 72-84 [Abstract] [Full Text]  
  • Song, M. J., Deng, H., Sun, R. (2003). Comparative Study of Regulation of RTA-Responsive Genes in Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8. J. Virol. 77: 9451-9462 [Abstract] [Full Text]  
  • Lee, B.-S., Connole, M., Tang, Z., Harris, N. L., Jung, J. U. (2003). Structural Analysis of the Kaposi's Sarcoma-Associated Herpesvirus K1 Protein. J. Virol. 77: 8072-8086 [Abstract] [Full Text]  
  • Dourmishev, L. A., Dourmishev, A. L., Palmeri, D., Schwartz, R. A., Lukac, D. M. (2003). Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 175-212 [Abstract] [Full Text]  
  • Guo, H.-G., Sadowska, M., Reid, W., Tschachler, E., Hayward, G., Reitz, M. (2003). Kaposi's Sarcoma-Like Tumors in a Human Herpesvirus 8 ORF74 Transgenic Mouse. J. Virol. 77: 2631-2639 [Abstract] [Full Text]  
  • Deng, H., Chu, J. T., Rettig, M. B., Martinez-Maza, O., Sun, R. (2002). Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression. Blood 100: 1919-1921 [Abstract] [Full Text]  
  • Dezube, B. J., Zambela, M., Sage, D. R., Wang, J.-F., Fingeroth, J. D. (2002). Characterization of Kaposi sarcoma-associated herpesvirus/human herpesvirus-8 infection of human vascular endothelial cells: early events. Blood 100: 888-896 [Abstract] [Full Text]  
  • Deng, H., Song, M. J., Chu, J. T., Sun, R. (2002). Transcriptional Regulation of the Interleukin-6 Gene of Human Herpesvirus 8 (Kaposi's Sarcoma-Associated Herpesvirus). J. Virol. 76: 8252-8264 [Abstract] [Full Text]  
  • Moses, A. V., Jarvis, M. A., Raggo, C., Bell, Y. C., Ruhl, R., Luukkonen, B. G. M., Griffith, D. J., Wait, C. L., Druker, B. J., Heinrich, M. C., Nelson, J. A., Fruh, K. (2002). Kaposi's Sarcoma-Associated Herpesvirus-Induced Upregulation of the c-kit Proto-Oncogene, as Identified by Gene Expression Profiling, Is Essential for the Transformation of Endothelial Cells. J. Virol. 76: 8383-8399 [Abstract] [Full Text]  
  • Song, M. J., Li, X., Brown, H. J., Sun, R. (2002). Characterization of Interactions between RTA and the Promoter of Polyadenylated Nuclear RNA in Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8. J. Virol. 76: 5000-5013 [Abstract] [Full Text]  
  • Oksenhendler, E., Boulanger, E., Galicier, L., Du, M.-Q., Dupin, N., Diss, T. C., Hamoudi, R., Daniel, M.-T., Agbalika, F., Boshoff, C., Clauvel, J.-P., Isaacson, P. G., Meignin, V. (2002). High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood 99: 2331-2336 [Abstract] [Full Text]  
  • Liu, C., Okruzhnov, Y., Li, H., Nicholas, J. (2001). Human Herpesvirus 8 (HHV-8)-Encoded Cytokines Induce Expression of and Autocrine Signaling by Vascular Endothelial Growth Factor (VEGF) in HHV-8-Infected Primary-Effusion Lymphoma Cell Lines and Mediate VEGF-Independent Antiapoptotic Effects. J. Virol. 75: 10933-10940 [Abstract] [Full Text]  
  • Ciufo, D. M., Cannon, J. S., Poole, L. J., Wu, F. Y., Murray, P., Ambinder, R. F., Hayward, G. S. (2001). Spindle Cell Conversion by Kaposi's Sarcoma-Associated Herpesvirus: Formation of Colonies and Plaques with Mixed Lytic and Latent Gene Expression in Infected Primary Dermal Microvascular Endothelial Cell Cultures. J. Virol. 75: 5614-5626 [Abstract] [Full Text]  
  • Song, M. J., Brown, H. J., Wu, T.-T., Sun, R. (2001). Transcription Activation of Polyadenylated Nuclear RNA by Rta in Human Herpesvirus 8/Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 75: 3129-3140 [Abstract] [Full Text]  
  • Li, H., Wang, H., Nicholas, J. (2001). Detection of Direct Binding of Human Herpesvirus 8-Encoded Interleukin-6 (vIL-6) to both gp130 and IL-6 Receptor (IL-6R) and Identification of Amino Acid Residues of vIL-6 Important for IL-6R-Dependent and -Independent Signaling. J. Virol. 75: 3325-3334 [Abstract] [Full Text]  
  • Aoki, Y., Yarchoan, R., Wyvill, K., Okamoto, S.-i., Little, R. F., Tosato, G. (2001). Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders. Blood 97: 2173-2176 [Abstract] [Full Text]  
  • Low, W., Harries, M., Ye, H., Du, M.-Q., Boshoff, C., Collins, M. (2001). Internal Ribosome Entry Site Regulates Translation of Kaposi's Sarcoma-Associated Herpesvirus FLICE Inhibitory Protein. J. Virol. 75: 2938-2945 [Abstract] [Full Text]  
  • Nicholas, J (2000). Evolutionary aspects of oncogenic herpesviruses. Mol. Pathol. 53: 222-237 [Abstract] [Full Text]  
  • Oksenhendler, E., Carcelain, G., Aoki, Y., Boulanger, E., Maillard, A., Clauvel, J.-P., Agbalika, F. (2000). High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric Castleman disease in HIV-infected patients. Blood 96: 2069-2073 [Abstract] [Full Text]  
  • Gradoville, L., Gerlach, J., Grogan, E., Shedd, D., Nikiforow, S., Metroka, C., Miller, G. (2000). Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50/Rta Protein Activates the Entire Viral Lytic Cycle in the HH-B2 Primary Effusion Lymphoma Cell Line. J. Virol. 74: 6207-6212 [Abstract] [Full Text]  
  • Mullberg, J., Geib, T., Jostock, T., Hoischen, S. H., Vollmer, P., Voltz, N., Heinz, D., Galle, P. R., Klouche, M., Rose-John, S. (2000). IL-6 Receptor Independent Stimulation of Human gp130 by Viral IL-6. J. Immunol. 164: 4672-4677 [Abstract] [Full Text]  
  • Parravicini, C., Chandran, B., Corbellino, M., Berti, E., Paulli, M., Moore, P. S., Chang, Y. (2000). Differential Viral Protein Expression in Kaposi’s Sarcoma-Associated Herpesvirus-Infected Diseases : Kaposi’s Sarcoma, Primary Effusion Lymphoma, and Multicentric Castleman’s Disease. Am. J. Pathol. 156: 743-749 [Abstract] [Full Text]  
  • Damania, B., Choi, J.-K., Jung, J. U. (2000). Signaling Activities of Gammaherpesvirus Membrane Proteins. J. Virol. 74: 1593-1601 [Full Text]  
  • Dupin, N., Diss, T. L., Kellam, P., Tulliez, M., Du, M.-Q., Sicard, D., Weiss, R. A., Isaacson, P. G., Boshoff, C. (2000). HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma. Blood 95: 1406-1412 [Abstract] [Full Text]  
  • Luppi, M., Barozzi, P., Maiorana, A., Trovato, R., Marasca, R., Morselli, M., Cagossi, K., Torelli, G. (1999). Expression of Cell-Homologous Genes of Human Herpesvirus-8 in Human Immunodeficiency Virus-Negative Lymphoproliferative Diseases. Blood 94: 2931-2933 [Abstract] [Full Text]  
  • Wong, S. W., Bergquam, E. P., Swanson, R. M., Lee, F. W., Shiigi, S. M., Avery, N. A., Fanton, J. W., Axthelm, M. K. (1999). Induction of B Cell Hyperplasia in Simian Immunodeficiency Virus-Infected Rhesus Macaques with the Simian Homologue of Kaposi's Sarcoma-Associated Herpesvirus. JEM 190: 827-840 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»