This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dourmishev, L. A. Articles by Lukac, D. M. Search for Related Content PubMed PubMed Citation Articles by Dourmishev, L. A. Articles by Lukac, D. M.

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Department of Dermatology, Medical University of Sofia, Sofia Bulgaria,¹ Department of Microbiology and Molecular Genetics, International Center for Public Health,² Dermatology, University of Medicine and Dentistry of New Jersey/New Jersey Medical School, Newark, New Jersey³

Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection.

This article has been cited by other articles:

• Ye, F.-C., Zhou, F.-C., Xie, J.-P., Kang, T., Greene, W., Kuhne, K., Lei, X.-F., Li, Q.-H., Gao, S.-J. (2008). Kaposi's Sarcoma-Associated Herpesvirus Latent Gene vFLIP Inhibits Viral Lytic Replication through NF-{kappa}B-Mediated Suppression of the AP-1 Pathway: a Novel Mechanism of Virus Control of Latency. J. Virol. 82: 4235-4249 [Abstract] [Full Text]  
• Abada, R., Dreyfuss-Grossman, T., Herman-Bachinsky, Y., Geva, H., Masa, S.-R., Sarid, R. (2008). SIAH-1 Interacts with the Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORF45 Protein and Promotes Its Ubiquitylation and Proteasomal Degradation. J. Virol. 82: 2230-2240 [Abstract] [Full Text]  
• Fonsato, V., Buttiglieri, S., Chiara Deregibus, M., Bussolati, B., Caselli, E., Di Luca, D., Camussi, G. (2008). PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype. Blood 111: 2806-2815 [Abstract] [Full Text]  
• Sivakumar, R., Sharma-Walia, N., Raghu, H., Veettil, M. V., Sadagopan, S., Bottero, V., Varga, L., Levine, R., Chandran, B. (2008). Kaposi's Sarcoma-Associated Herpesvirus Induces Sustained Levels of Vascular Endothelial Growth Factors A and C Early during In Vitro Infection of Human Microvascular Dermal Endothelial Cells: Biological Implications. J. Virol. 82: 1759-1776 [Abstract] [Full Text]  
• Kuang, E., Tang, Q., Maul, G. G., Zhu, F. (2008). Activation of p90 Ribosomal S6 Kinase by ORF45 of Kaposi's Sarcoma-Associated Herpesvirus and Its Role in Viral Lytic Replication. J. Virol. 82: 1838-1850 [Abstract] [Full Text]  
• Palmeri, D., Spadavecchia, S., Carroll, K. D., Lukac, D. M. (2007). Promoter- and Cell-Specific Transcriptional Transactivation by the Kaposi's Sarcoma-Associated Herpesvirus ORF57/Mta Protein. J. Virol. 81: 13299-13314 [Abstract] [Full Text]  
• Lan, K., Verma, S. C., Murakami, M., Bajaj, B., Kaul, R., Robertson, E. S. (2007). Kaposi's sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by targeting the Sel10 protein. Proc. Natl. Acad. Sci. USA 104: 16287-16292 [Abstract] [Full Text]  
• Cai, Q., Murakami, M., Si, H., Robertson, E. S. (2007). A Potential {alpha}-Helix Motif in the Amino Terminus of LANA Encoded by Kaposi's Sarcoma-Associated Herpesvirus Is Critical for Nuclear Accumulation of HIF-1{alpha} in Normoxia. J. Virol. 81: 10413-10423 [Abstract] [Full Text]  
• Vider-Shalit, T., Fishbain, V., Raffaeli, S., Louzoun, Y. (2007). Phase-Dependent Immune Evasion of Herpesviruses. J. Virol. 81: 9536-9545 [Abstract] [Full Text]  
• Carroll, K. D., Khadim, F., Spadavecchia, S., Palmeri, D., Lukac, D. M. (2007). Direct Interactions of Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Protein with the Cellular Protein Octamer-1 and DNA Are Critical for Specifying Transactivation of a Delayed-Early Promoter and Stimulating Viral Reactivation. J. Virol. 81: 8451-8467 [Abstract] [Full Text]  
• Rose, P. P., Bogyo, M., Moses, A. V., Fruh, K. (2007). Insulin-Like Growth Factor II Receptor-Mediated Intracellular Retention of Cathepsin B Is Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 81: 8050-8062 [Abstract] [Full Text]  
• Raghu, H., Sharma-Walia, N., Veettil, M. V., Sadagopan, S., Caballero, A., Sivakumar, R., Varga, L., Bottero, V., Chandran, B. (2007). Lipid Rafts of Primary Endothelial Cells Are Essential for Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8-Induced Phosphatidylinositol 3-Kinase and RhoA-GTPases Critical for Microtubule Dynamics and Nuclear Delivery of Viral DNA but Dispensable for Binding and Entry. J. Virol. 81: 7941-7959 [Abstract] [Full Text]  
• Duprez, R., Lacoste, V., Briere, J., Couppie, P., Frances, C., Sainte-Marie, D., Kassa-Kelembho, E., Lando, M.-J., Essame Oyono, J.-L., Nkegoum, B., Hbid, O., Mahe, A., Lebbe, C., Tortevoye, P., Huerre, M., Gessain, A. (2007). Evidence for a Multiclonal Origin of Multicentric Advanced Lesions of Kaposi Sarcoma. JNCI J Natl Cancer Inst 99: 1086-1094 [Abstract] [Full Text]  
• Qian, L.-W., Xie, J., Ye, F., Gao, S.-J. (2007). Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases. J. Virol. 81: 7001-7010 [Abstract] [Full Text]  
• Xu, D., Coleman, T., Zhang, J., Fagot, A., Kotalik, C., Zhao, L., Trivedi, P., Jones, C., Zhang, L. (2007). Epstein-Barr Virus Inhibits Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication in Primary Effusion Lymphomas. J. Virol. 81: 6068-6078 [Abstract] [Full Text]  
• Bu, W., Carroll, K. D., Palmeri, D., Lukac, D. M. (2007). Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Lytic Switch Protein Functions as a Tetramer. J. Virol. 81: 5788-5806 [Abstract] [Full Text]  
• Sadagopan, S., Sharma-Walia, N., Veettil, M. V., Raghu, H., Sivakumar, R., Bottero, V., Chandran, B. (2007). Kaposi's Sarcoma-Associated Herpesvirus Induces Sustained NF-{kappa}B Activation during De Novo Infection of Primary Human Dermal Microvascular Endothelial Cells That Is Essential for Viral Gene Expression. J. Virol. 81: 3949-3968 [Abstract] [Full Text]  
• Ye, F.-C., Blackbourn, D. J., Mengel, M., Xie, J.-P., Qian, L.-W., Greene, W., Yeh, I-T., Graham, D., Gao, S.-J. (2007). Kaposi's Sarcoma-Associated Herpesvirus Promotes Angiogenesis by Inducing Angiopoietin-2 Expression via AP-1 and Ets1. J. Virol. 81: 3980-3991 [Abstract] [Full Text]  
• Nascimento, M. C., de Souza, V. A., Sumita, L. M., Freire, W., Munoz, F., Kim, J., Pannuti, C. S., Mayaud, P. (2007). Comparative Study of Kaposi's Sarcoma-Associated Herpesvirus Serological Assays Using Clinically and Serologically Defined Reference Standards and Latent Class Analysis. J. Clin. Microbiol. 45: 715-720 [Abstract] [Full Text]  
• Zhu, F. X., Li, X., Zhou, F., Gao, S.-J., Yuan, Y. (2006). Functional Characterization of Kaposi's Sarcoma-Associated Herpesvirus ORF45 by Bacterial Artificial Chromosome-Based Mutagenesis. J. Virol. 80: 12187-12196 [Abstract] [Full Text]  
• Veettil, M. V., Sharma-Walia, N., Sadagopan, S., Raghu, H., Sivakumar, R., Naranatt, P. P., Chandran, B. (2006). RhoA-GTPase Facilitates Entry of Kaposi's Sarcoma-Associated Herpesvirus into Adherent Target Cells in a Src-Dependent Manner. J. Virol. 80: 11432-11446 [Abstract] [Full Text]  
• Lisco, A., Barbierato, M., Fiore, J. R., Gasperini, P., Favia, A., Volpe, A., Chironna, M., Pastore, G., Chieco-Bianchi, L., Calabro, M. L. (2006). Pregnancy and Human Herpesvirus 8 Reactivation in Human Immunodeficiency Virus Type 1-Infected Women. J. Clin. Microbiol. 44: 3863-3871 [Abstract] [Full Text]  
• Lan, K., Choudhuri, T., Murakami, M., Kuppers, D. A., Robertson, E. S. (2006). Intracellular Activated Notch1 Is Critical for Proliferation of Kaposi's Sarcoma-Associated Herpesvirus-Associated B-Lymphoma Cell Lines In Vitro.. J. Virol. 80: 6411-6419 [Abstract] [Full Text]  
• Sharma-Walia, N., Raghu, H., Sadagopan, S., Sivakumar, R., Veettil, M. V., Naranatt, P. P., Smith, M. M., Chandran, B. (2006). Cyclooxygenase 2 Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during In Vitro Infection of Target Cells Plays a Role in the Maintenance of Latent Viral Gene Expression.. J. Virol. 80: 6534-6552 [Abstract] [Full Text]  
• Lu, F., Day, L., Gao, S.-J., Lieberman, P. M. (2006). Acetylation of the Latency-Associated Nuclear Antigen Regulates Repression of Kaposi's Sarcoma-Associated Herpesvirus Lytic Transcription.. J. Virol. 80: 5273-5282 [Abstract] [Full Text]  
• Pan, H., Xie, J., Ye, F., Gao, S.-J. (2006). Modulation of Kaposi's Sarcoma-Associated Herpesvirus Infection and Replication by MEK/ERK, JNK, and p38 Multiple Mitogen-Activated Protein Kinase Pathways during Primary Infection.. J. Virol. 80: 5371-5382 [Abstract] [Full Text]  
• Cohen, A., Brodie, C., Sarid, R. (2006). An essential role of ERK signalling in TPA-induced reactivation of Kaposi's sarcoma-associated herpesvirus.. J. Gen. Virol. 87: 795-802 [Abstract] [Full Text]  
• Krishnan, H. H., Sharma-Walia, N., Streblow, D. N., Naranatt, P. P., Chandran, B. (2006). Focal Adhesion Kinase Is Critical for Entry of Kaposi's Sarcoma-Associated Herpesvirus into Target Cells. J. Virol. 80: 1167-1180 [Abstract] [Full Text]  
• Xie, J., Pan, H., Yoo, S., Gao, S.-J. (2005). Kaposi's Sarcoma-Associated Herpesvirus Induction of AP-1 and Interleukin 6 during Primary Infection Mediated by Multiple Mitogen-Activated Protein Kinase Pathways. J. Virol. 79: 15027-15037 [Abstract] [Full Text]  
• Pearce, M., Matsumura, S., Wilson, A. C. (2005). Transcripts Encoding K12, v-FLIP, v-Cyclin, and the MicroRNA Cluster of Kaposi's Sarcoma-Associated Herpesvirus Originate from a Common Promoter. J. Virol. 79: 14457-14464 [Abstract] [Full Text]  
• Madureira, P. A., Matos, P., Soeiro, I., Dixon, L. K., Simas, J. P., Lam, E. W.-F. (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 [Abstract] [Full Text]  
• Wakenshaw, L., Walters, M. S., Whitehouse, A. (2005). The Herpesvirus Saimiri Replication and Transcription Activator Acts Synergistically with CCAAT Enhancer Binding Protein Alpha To Activate the DNA Polymerase Promoter. J. Virol. 79: 13548-13560 [Abstract] [Full Text]  
• Wong, L.-Y., Wilson, A. C. (2005). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Induces a Strong Bend on Binding to Terminal Repeat DNA. J. Virol. 79: 13829-13836 [Abstract] [Full Text]  
• Lu, F., Day, L., Lieberman, P. M. (2005). Kaposi's Sarcoma-Associated Herpesvirus Virion-Induced Transcription Activation of the ORF50 Immediate-Early Promoter. J. Virol. 79: 13180-13185 [Abstract] [Full Text]  
• Thijsen, S. F. T., Luderer, R., van Gorp, J. M. H., Oudejans, S. J. G., Bossink, A. W. J. (2005). A possible role for Epstein-Barr virus in the pathogenesis of pleural effusion. Eur Respir J 26: 662-666 [Abstract] [Full Text]  
• Chugh, P., Matta, H., Schamus, S., Zachariah, S., Kumar, A., Richardson, J. A., Smith, A. L., Chaudhary, P. M. (2005). Constitutive NF-{kappa}B activation, normal Fas-induced apoptosis, and increased incidence of lymphoma in human herpes virus 8 K13 transgenic mice. Proc. Natl. Acad. Sci. USA 102: 12885-12890 [Abstract] [Full Text]  
• Krishnan, H. H., Sharma-Walia, N., Zeng, L., Gao, S.-J., Chandran, B. (2005). Envelope Glycoprotein gB of Kaposi's Sarcoma-Associated Herpesvirus Is Essential for Egress from Infected Cells. J. Virol. 79: 10952-10967 [Abstract] [Full Text]  
• Sharma-Walia, N., Krishnan, H. H., Naranatt, P. P., Zeng, L., Smith, M. S., Chandran, B. (2005). ERK1/2 and MEK1/2 Induced by Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Early during Infection of Target Cells Are Essential for Expression of Viral Genes and for Establishment of Infection. J. Virol. 79: 10308-10329 [Abstract] [Full Text]  
• Matsumura, S., Fujita, Y., Gomez, E., Tanese, N., Wilson, A. C. (2005). Activation of the Kaposi's Sarcoma-Associated Herpesvirus Major Latency Locus by the Lytic Switch Protein RTA (ORF50). J. Virol. 79: 8493-8505 [Abstract] [Full Text]  
• Al Mehairi, S., Cerasoli, E., Sinclair, A. J. (2005). Investigation of the Multimerization Region of the Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Protein K-bZIP: the Proposed Leucine Zipper Region Encodes a Multimerization Domain with an Unusual Structure. J. Virol. 79: 7905-7910 [Abstract] [Full Text]  
• Gasperini, P., Barbierato, M., Martinelli, C., Rigotti, P., Marchini, F., Masserizzi, G., Leoncini, F., Chieco-Bianchi, L., Schulz, T. F., Calabro, M. L. (2005). Use of a BJAB-Derived Cell Line for Isolation of Human Herpesvirus 8. J. Clin. Microbiol. 43: 2866-2875 [Abstract] [Full Text]  
• Cheung, M. C., Pantanowitz, L., Dezube, B. J. (2005). AIDS-Related Malignancies: Emerging Challenges in the Era of Highly Active Antiretroviral Therapy. The Oncologist 10: 412-426 [Abstract] [Full Text]  
• Cameron, C. M., Barrett, J. W., Liu, L., Lucas, A. R., McFadden, G. (2005). Myxoma Virus M141R Expresses a Viral CD200 (vOX-2) That Is Responsible for Down-Regulation of Macrophage and T-Cell Activation In Vivo. J. Virol. 79: 6052-6067 [Abstract] [Full Text]  
• Prakash, O., Swamy, O. R., Peng, X., Tang, Z.-Y., Li, L., Larson, J. E., Cohen, J. C., Gill, J., Farr, G., Wang, S., Samaniego, F. (2005). Activation of Src kinase Lyn by the Kaposi sarcoma-associated herpesvirus K1 protein: implications for lymphomagenesis. Blood 105: 3987-3994 [Abstract] [Full Text]  
• Zhang, J., Wang, J., Wood, C., Xu, D., Zhang, L. (2005). Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 Replication and Transcription Activator Regulates Viral and Cellular Genes via Interferon-Stimulated Response Elements. J. Virol. 79: 5640-5652 [Abstract] [Full Text]  
• Wang, J., Zhang, J., Zhang, L., Harrington, W. Jr., West, J. T., Wood, C. (2005). Modulation of Human Herpesvirus 8/Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Activator Transactivation by Interferon Regulatory Factor 7. J. Virol. 79: 2420-2431 [Abstract] [Full Text]  
• Malik, P., Clements, J. B. (2004). Protein kinase CK2 phosphorylation regulates the interaction of Kaposi's sarcoma-associated herpesvirus regulatory protein ORF57 with its multifunctional partner hnRNP K. Nucleic Acids Res 32: 5553-5569 [Abstract] [Full Text]  
• Wong, L.-Y., Matchett, G. A., Wilson, A. C. (2004). Transcriptional Activation by the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Is Facilitated by an N-Terminal Chromatin-Binding Motif. J. Virol. 78: 10074-10085 [Abstract] [Full Text]  
• Malik, P., Blackbourn, D. J., Cheng, M. F., Hayward, G. S., Clements, J. B. (2004). Functional co-operation between the Kaposi's sarcoma-associated herpesvirus ORF57 and ORF50 regulatory proteins. J. Gen. Virol. 85: 2155-2166 [Abstract] [Full Text]  
• Malik, P., Blackbourn, D. J., Clements, J. B. (2004). The Evolutionarily Conserved Kaposi's Sarcoma-associated Herpesvirus ORF57 Protein Interacts with REF Protein and Acts as an RNA Export Factor. J. Biol. Chem. 279: 33001-33011 [Abstract] [Full Text]  
• Verzijl, D., Fitzsimons, C. P., van Dijk, M., Stewart, J. P., Timmerman, H., Smit, M. J., Leurs, R. (2004). Differential Activation of Murine Herpesvirus 68- and Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORF74 G Protein-Coupled Receptors by Human and Murine Chemokines. J. Virol. 78: 3343-3351 [Abstract] [Full Text]  
• Krishnan, H. H., Naranatt, P. P., Smith, M. S., Zeng, L., Bloomer, C., Chandran, B. (2004). Concurrent Expression of Latent and a Limited Number of Lytic Genes with Immune Modulation and Antiapoptotic Function by Kaposi's Sarcoma-Associated Herpesvirus Early during Infection of Primary Endothelial and Fibroblast Cells and Subsequent Decline of Lytic Gene Expression. J. Virol. 78: 3601-3620 [Abstract] [Full Text]  
• Gillet, L., Minner, F., Detry, B., Farnir, F., Willems, L., Lambot, M., Thiry, E., Pastoret, P.-P., Schynts, F., Vanderplasschen, A. (2004). Investigation of the Susceptibility of Human Cell Lines to Bovine Herpesvirus 4 Infection: Demonstration that Human Cells Can Support a Nonpermissive Persistent Infection Which Protects Them against Tumor Necrosis Factor Alpha-Induced Apoptosis. J. Virol. 78: 2336-2347 [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]  
• Matta, H., Sun, Q., Moses, G., Chaudhary, P. M. (2003). Molecular Genetic Analysis of Human Herpes Virus 8-encoded Viral FLICE Inhibitory Protein-induced NF-{kappa}B Activation. J. Biol. Chem. 278: 52406-52411 [Abstract] [Full Text]  
• Dadke, D., Fryer, B. H., Golemis, E. A., Field, J. (2003). Activation of p21-Activated Kinase 1-Nuclear Factor {kappa}B Signaling by Kaposi's Sarcoma-Associated Herpes Virus G Protein-Coupled Receptor during Cellular Transformation. Cancer Res. 63: 8837-8847 [Abstract] [Full Text]