The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen

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J. Virol., Aug 1997, 5915-5921, Vol 71, No. 8
Copyright © 1997, American Society for Microbiology

The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen

L Rainbow, GM Platt, GR Simpson, R Sarid, SJ Gao, H Stoiber, CS Herrington, PS Moore and TF Schulz
Department of Medical Microbiology and Genitourinary Medicine, The University of Liverpool, United Kingdom.

Kaposi's sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (KSHV/HHV8) is the likely cause of KS and primary effusion lymphomas or body cavity-based lymphomas (BCBLs). A latency-associated nuclear immunofluorescence antigen (LANA) (D. H. Kedes, E. Operskalski, M. Busch, R. Kohn, J. Flood, and D. Ganem, Nat. Med. 2:918-924, 1996; S. J. Gao, L. Kingsley, M. Li, W. Zheng, C. Parravicini, J. Ziegler, R. Newton, C. R. Rinaldo, A. Saah, J. Phair, R. Detels, Y. Chang, and P. S. Moore, Nat. Med. 2:925-928, 1996) and a 222- to 234-kDa nuclear protein (LNA) (S. J. Gao, L. Kingsley, D. R. Hoover, T. J. Spira, C. R. Rinaldo, A. Saah, J. Phair, R. Detels, P. Parry, Y. Chang, and P. S. Moore, N. Engl. J. Med. 335:233-241, 1996) have previously been described in BCBL cell lines by immunofluorescence and Western blotting techniques, respectively. To identify the viral gene(s) encoding this antigen(s) we screened a cDNA library from HBL-6 cells, a B-cell lymphoma cell line persistently infected with KSHV/HHV8, with KS patient sera. One set of positive clones contained the 3' end of orf73, as well as the complete orf72 and orfK13, and another set contained the 5' end of orf73. Comparison of cDNA sequences with the KSHV/HHV8 genomic sequence revealed a splice event, occurring upstream of orf73. Immunoaffinity purified antibodies to a recombinant carboxy-terminal fragment of the orf73-encoded protein showed the characteristic speckled nuclear immunofluorescence pattern of LANA and reacted with the 222- to 234-kDa LNA on Western blots. Expression of full-length orf73 in bacteria and COS7 cells reproduced the LNA banding pattern. Immunohistochemistry on cases of nodular KS revealed that orf73/LNA is expressed in the nucleus of KS spindle cells. These findings demonstrate that orf73 encodes the 222- to 234-kDa LNA, is a component of LANA, and is expressed in KS tumor cells.

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Liu, L., Eby, M. T., Rathore, N., Sinha, S. K., Kumar, A., Chaudhary, P. M. (2002). The Human Herpes Virus 8-encoded Viral FLICE Inhibitory Protein Physically Associates with and Persistently Activates the Ikappa B Kinase Complex. J. Biol. Chem. 277: 13745-13751 [Abstract] [Full Text]
Pertel, P. E. (2002). Human Herpesvirus 8 Glycoprotein B (gB), gH, and gL Can Mediate Cell Fusion. J. Virol. 76: 4390-4400 [Abstract] [Full Text]
Chiou, C.-J., Poole, L. J., Kim, P. S., Ciufo, D. M., Cannon, J. S., ap Rhys, C. M., Alcendor, D. J., Zong, J.-C., Ambinder, R. F., Hayward, G. S. (2002). Patterns of Gene Expression and a Transactivation Function Exhibited by the vGCR (ORF74) Chemokine Receptor Protein of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 76: 3421-3439 [Abstract] [Full Text]
Coulter, L. J., Reid, H. W. (2002). Isolation and expression of three open reading frames from ovine herpesvirus-2. J. Gen. Virol. 83: 533-543 [Abstract] [Full Text]
Lagunoff, M., Bechtel, J., Venetsanakos, E., Roy, A.-M., Abbey, N., Herndier, B., McMahon, M., Ganem, D. (2002). De Novo Infection and Serial Transmission of Kaposi's Sarcoma-Associated Herpesvirus in Cultured Endothelial Cells. J. Virol. 76: 2440-2448 [Abstract] [Full Text]
An, J., Lichtenstein, A. K., Brent, G., Rettig, M. B. (2002). The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element. Blood 99: 649-654 [Abstract] [Full Text]
Mattsson, K., Kiss, C., Platt, G. M., Simpson, G. R., Kashuba, E., Klein, G., Schulz, T. F., Szekely, L. (2002). Latent nuclear antigen of Kaposi's sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions. J. Gen. Virol. 83: 179-188 [Abstract] [Full Text]
Groves, A. K., Cotter, M. A., Subramanian, C., Robertson, E. S. (2001). The Latency-Associated Nuclear Antigen Encoded by Kaposi's Sarcoma-Associated Herpesvirus Activates Two Major Essential Epstein-Barr Virus Latent Promoters. J. Virol. 75: 9446-9457 [Abstract] [Full Text]
Kakoola, D. N., Sheldon, J., Byabazaire, N., Bowden, R. J., Katongole-Mbidde, E., Schulz, T. F., Davison, A. J. (2001). Recombination in human herpesvirus-8 strains from Uganda and evolution of the K15 gene. J. Gen. Virol. 82: 2393-2404 [Abstract] [Full Text]
Garber, A. C., Shu, M. A., Hu, J., Renne, R. (2001). DNA Binding and Modulation of Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 75: 7882-7892 [Abstract] [Full Text]
Piolot, T., Tramier, M., Coppey, M., Nicolas, J.-C., Marechal, V. (2001). Close but Distinct Regions of Human Herpesvirus 8 Latency-Associated Nuclear Antigen 1 Are Responsible for Nuclear Targeting and Binding to Human Mitotic Chromosomes. J. Virol. 75: 3948-3959 [Abstract] [Full Text]
Ballestas, M. E., Kaye, K. M. (2001). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mediates Episome Persistence through cis-Acting Terminal Repeat (TR) Sequence and Specifically Binds TR DNA. J. Virol. 75: 3250-3258 [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]
Pitha, P. M. (2001). Latently Expressed Human Herpesvirus 8-Encoded Interferon Regulatory Factor 2 Inhibits Double-Stranded RNA-Activated Protein Kinase. J. Virol. 75: 2345-2352 [Abstract] [Full Text]
Jeong, J., Papin, J., Dittmer, D. (2001). Differential Regulation of the Overlapping Kaposi's Sarcoma-Associated Herpesvirus vGCR (orf74) and LANA (orf73) Promoters. J. Virol. 75: 1798-1807 [Abstract] [Full Text]
Vieira, J., O'Hearn, P., Kimball, L., Chandran, B., Corey, L. (2001). Activation of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Lytic Replication by Human Cytomegalovirus. J. Virol. 75: 1378-1386 [Abstract] [Full Text]
Rivas, C., Thlick, A.-E., Parravicini, C., Moore, P. S., Chang, Y. (2001). Kaposi's Sarcoma-Associated Herpesvirus LANA2 Is a B-Cell-Specific Latent Viral Protein That Inhibits p53. J. Virol. 75: 429-438 [Abstract] [Full Text]
Renne, R., Barry, C., Dittmer, D., Compitello, N., Brown, P. O., Ganem, D. (2001). Modulation of Cellular and Viral Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 75: 458-468 [Abstract] [Full Text]
Luppi, M., Barozzi, P., Schulz, T. F., Setti, G., Staskus, K., Trovato, R., Narni, F., Donelli, A., Maiorana, A., Marasca, R., Sandrini, S., Torelli, G., Sheldon, J. (2000). Bone Marrow Failure Associated with Human Herpesvirus 8 Infection after Transplantation. NEJM 343: 1378-1385 [Abstract] [Full Text]
Lim, C., Sohn, H., Gwack, Y., Choe, J. (2000). Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) binds ATF4/CREB2 and inhibits its transcriptional activation activity. J. Gen. Virol. 81: 2645-2652 [Abstract] [Full Text]

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