Kaposi’s sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV 8), is the infectious cause of Kaposi’s sarcoma (KS), an endothelial cell derived vascular tumour. KS is frequently found in AIDS patients and now represents the most common cancer in Africa. In addition, KS plays a role in transplant recipients originating in those countries where KSHV/HHV8 is more prevalent (see below). KSHV/HHV8 is also important in the pathogenesis of the plasma cell variant of Multicentric Castleman’s Disease (MCD) and is probably essential for the development of primary effusion lymphoma (PEL). KSHV/HHV8 was discovered by Yuan Chang and Patrick Moore in 1994 and has now been recognized by the International Agency for Research against Cancer (IARC) as one of 6 known human tumour viruses.

Like all herpesviruses, KSHV/HHV8 persists for the lifetime of an infected individual. During this life-long persistence the virus may exist in a non-replicative form, in which no new virus progeny is produced, and only the viral genome is maintained in infected cells. Periodically the virus may reactivate, produce new viral offspring, which is then shed and may infect other individuals or new cells of the same individual. Our research aims to understand the mechanisms that allow the virus to establish such a latent infection or to reactivate. We are particularly interested in the function of two viral proteins:

(i) the latency associated nuclear antigen (LANA-1) which plays a role in the replication of the latent viral genome and (ii) a family of proteins encoded by the K15 gene of KSHV/HHV8 which resemble the latent membrane proteins of another human tumorigenic herpesvirus, Epstein-Barr virus.

KSHV/HHV8 is apparently an ‘old’ human virus which has infected humans since the origins of Homo sapiens. We are trying to understand why this virus has become rare in many parts of the world and how it is transmitted in those countries where primary infection occurs mainly in childhood. This is the case in subsaharan Africa, in some regions of Mediterranean countries, and in some populations in South America. In this context we are also interested in related viruses found in non-human primates: most Old World and several New World non-human primates harbour viruses that are closely related to KSHV/HHV8. By studying their relationship to KSHV/HHV8 we try to refine molecular biology based techniques for the detection of hitherto unknown viruses. By studying the differences between viral genomes we try to gain some insight into which KSHV/HHV8 genes are responsible for its pathogenic properties.

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    +49 511 532 6736 | Schulz.Thomas@MH-Hannover.De

Dr. Schulz qualified as a medical doctor in Mainz (1979), obtained his MD in 1980 and initially worked in Internal Medicine. He trained as a medical microbiologist in the Department of Medical Microbiology in Mainz (1981 - 1983) and the Institute of Hygiene in Innsbruck (1983 - 1988). Having completed a postdoctoral thesis ("Habilitation") in 1986, he joined Prof. Robin Weiss’ group at the Institute of Cancer Research, London, as an EMBO Fellow in 1988. From 1988 until 1995 he worked mainly on HIV-1,2, HTLV-I and KSHV/HHV8 (from 1994). In 1995 he was appointed to a professorial chair in the Dept. Medical Microbiology of The University of Liverpool, where he worked on KSHV/HHV8. Since 2000 he has been heading the Institute of Virology of Hannover Medical School in Hannover, Germany.

Since 1997 Dr. Schulz has been the editor for retroviruses of The Journal of General Virology.

    +49 511 532 4323, 8323 o. 6493 | Brinkmann.Melanie@MH-Hannover.de

    +49 511 532 4307 | Engelmann.Ilka@MH-Hannover.de

    +49 511 532 4307 | Henke-Gendo.Cornelia@MH-Hannover.De

    +49 511 532 4324 | Bruening.Eva@MH-Hannover.De

    +49 511 532 4324 | Hartmann.Silke@MH-Hannover.De

    +49 511 532 4324 | Ottinger.Matthias@MH-Hannover.De

Khaled Al-Kharsah, MSc; PhD student | +49 511 532 4324

Linding, Wang, MSc, PhD student | +49 511 532 4324

Emrah Kati | +49 511 532 4324

Merle Schmidt | +49 511 532 4324

    +49 511 532 4324 | Fischer.Irina@MH-Hannover.De

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Research of our group is mainly funded by the German Research Council in the form of a project grant (Schu-1436/1-1), a graduate research programme (Graduierten Kolleg; GK 745) and a research co-operative "Infections of endothelial cells" (Schwerpunktprogramm Infektionen des Endothels; Schu 1436/2 - 1). Dr. Martin Dedicoat is supported by a Clinical Tropical Fellowship of the Wellcome Trust, London, held at the Liverpool School of Tropical Medicine.

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Boshoff,C., Whitby,D., Hatziioannou, T., Fisher, C., van der Walt, J., Hatzakis, A., Weiss, R.A., Schulz, T.F. (1995). "Presence of Kaposi’s Sarcoma - Associated Herpes Virus in HIV negative Kaposi’s Sarcoma." Lancet 345: 1043 - 1044.

Whitby,D., Howard,M.R., Tenant-Flowrs,M., Brink,N.S., Copas,A., Boshoff,C., Hatzioannou,T., Suggett,F.E.A., Aldam, D.M., Denton,A.S., Miller,R.F., Weller, I.V.D., Weiss,R.A., Tedder,R.S., Schulz, T.F.(1995) "Detection of Kaposi's sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma." Lancet 346:799-802.

Boshoff,C., Schulz, T.F., Kennedy,M.M., Graham, A.K., Fisher, C., Thomas, A., McGee, J. O'D, Weiss, R.A., O'Leary, J.J. (1995) "Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells." Nature Medicine 1: 1274-1278

Boshoff, C., Talbot, S., Kennedy, M., O'Leary, J.J., Schulz, T.F., Chang, Y. (1996) HHV 8 and skin cancers in immunosuppressed patients. Lancet 347: 388 - 389

Chang, Y., Ziegler, J., Wabinga, H., Katangole-Mbidde, E., Boshoff, C., Schulz, T.F., Whitby,D., Maddalena,D., Jaffe, H.W., Weiss, R.A., The Uganda Kaposi's sarcoma study group, Moore, P.S. (1996). "Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa." Archives of Internal Medicine 156: 202 - 204

Pawson,R., Catovsky, D., Schulz, T.F.(1996) "Lack of evidence of HHV-8 in mature T-cell lymphoproliferative disorders." Lancet 348: 1450 - 1451

Simpson, G.R., Schulz,T.F., Whitby,D., Cook,P.M., Boshoff, C., Rainbow, L., Howard, M., Gao, S.-J., Bohenzky, R.A., Simmonds, P., Lee, C., de Ruiter, A., Hatzakis, A., Tedder, R.S., Weller, I.V.D., Weiss, R.A., Moore, P.S. (1996) "Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen." Lancet 348:1133 - 1138

Howard, M., Whitby, D., Bahadur, G., Suggett, F., Boshoff, C., Tenant-Flowers, M., Schulz, T.F., Kirk, S., Matthews, S., Weller, I.V.D., Tedder, R.S., Weiss, R.A. (1997) "Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but not healthy semen donors." AIDS 11: F15 - F19

Blauvelt,A., Sei,S., Cook, P.M., Schulz, T.F., Jeang, K.-T. (1997) Human herpesvirus 8 infection occurs following adolescence in the United States. J.Inf. Dis. 176:771 - 774

Cook, P.M., Rascu, A., Calden, J.R., Schulz, T.F., Harrer, T. (1997) "No serological evidence for an involvement of human herpesvirus 8 in autoimmune diseases." Arthritis and Rheumatism 40: 1906-1907

Rainbow, L., Platt, G.M., Simpson, G.R., Sarid, R., Gao, S.-J., Stoiber, H., Herringston, C.S., Moore, P.S., Schulz, T.F.(1997). "The 222-234 kd nuclear protein (LNA) of Kaposi's sarcoma - associated herpesvirus (KSHV/HHV 8) is encoded by orf73 and a component of the latency-associated nuclear antigen (LANA)." J.Virol. 71: 5915-5921

Pawson,R., Schulz, T.F., Matutes, E., Catovsky, D. (1997) "The human T-cell lymphotropic viruses types I/II are not involved in T prolymphocytic leukemia and large granular lymphocytic leukemia." Leukemia 11: 1305-1311

MacKenzie, J., Sheldon, J., Morgan, G., Cook, G., Schulz, T.F., Jarrett, R.F. (1997) "HHV-8 and multiple myeloma in the UK." Lancet 350: 1144 - 1145

Monini, P., Howard, M., Rimessi, P., de Lellis, L., Schulz, T.F., Cassai, E. (1997) "Human herpesvirus DNA in prostate and semen from HIV-negative individuals in Italy." AIDS 11: 1530 - 1531

Calabrò, M.L., Sheldon, J., Favero, A., Simpson, G.R., Fiore, J.R., Gomes, E., Angarano, G., Chieco-Bianchi, L., Schulz, T.F.(1998) "Seroprevalence of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in different regions of Italy." J.Hum. Virol. 1:207 - 213

Ariyoshi,K., Schim van der Loeff, M., Cook, P.M., Whitby, D.,, Corrah, T., Jaffar, S., Cham, F., Sabally, S., O’Donovan, D., Weiss, R.A., Schulz, T.F., Whittle, H. (1998). "Kaposi's sarcoma and human herpesvirus 8 (HHV8) in HIV-1 and HIV-2 infection in The Gambia." J.Hum.Virol 1: 193 - 199

Oksenhendler, E., Cazals-Hatem,D., Schulz, T.F., Barateau, V., Grollet, L., Sheldon, J., Clauvel, J.-P., Sigaux, F., Agbalika, F. (1998). "Transient angiolymphoid hyperplasia and Kaposi’s sarcoma following primary infection with human herpesvirus 8 in a patient with HIV infection." N.Engl. J. Med. 338:1585 - 1590

Melbye,M., Cook, P.M., Hjalgrim, H., Begtrup, K., Simpson, G.R., Biggar, R.J., Ebbesen, P., Schulz, T.F.(1998). "Risk factors for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) seropositivity in a cohort of homosexual men, 1981 - 1996." Int. J. Cancer, 77: 543-548

Mayama, S., Cuevas, L., Sheldon, J., Smith,D., Okong,P., Silvel,B., Schulz, T.F.(1998). "revalence of Kaposi’s sarcoma associated herpesvirus (Human herpesvirus 8) in a young Ugandan population." Int. J. Cancer, 77: 817-820

Rabkin, C.S., Schulz, T.F., Whitby, D., Lennette, E.T., Magpanty, L.I., Chatlynne, L., Biggar, R.J. (1998) "Interassay correlation of human herpesvirus 8 (HHV-8) serologic tests." J. Infectious Diseases, 178:304-309

Mitterer, M., Mair, W., Gatti,D., Sheldon,J., Vachula,M., Coser, P., Schulz, T.F.(1998) "Dendritic cells derived from bone marrow and CD34+ selected blood progenitor cells of myeloma patients, cultured in serum-free media, do not contain the Kaposi sarcoma herpesvirus genome." Br. J. Haematol. 102: 1338 - 1340

Renwick, N., Halaby, T., Weverling, G.J., Simpson, G.R., Coutinho, R.A., Lange, J.M.A., Schulz, T.F., Goudsmit, J. (1998) "Seroconversion for Kaposi’s sarcoma-associated herpesvirus is highly predictive of KS development in HIV-1 infected individuals." AIDS 12: 2481 - 2488

Lebbé, C., Agbalika,F., Flageul,B., Pellet,C., Rybojad,M., Cordoliani,F., Farge,D., Vignon-Pennamen,M.D., Morel,P., Calvo,F., Schulz, T.F.(1999) "No evidence for a role of HHV8 in sarcoidosis: molecular and serologic analysis." Br. J. Dermatol. 141: 492 - 496

Tedeschi,R., De Paoli, P., Schulz, T.F., Dillner, J. (1999) "Human serum antibodies to a major defined epitope of the human herpesvirus type 8 small viral capsid protein." J.Inf.Dis. . 197: 1016 - 1020

Farge, D., Lebbé, C., Marjanovic, Z., Tuppin, P., Mouquet, C. Peraldi, M.-N., Lang, P., Hiesse, C., Antoine, C., Legendre, C., Bedrossian, J., Gagnadoux, M.F., Loirat, C., Pellet, C., Sheldon, J., Golmard, J.-L., Agbalika, F., Schulz, T.F.(1999) "Human herpesvirus 8 (HHV 8) and other risk factors for Kaposi’s sarcoma in kidney transplant recipients." Transplantation 67: 1236 - 1242

Sachsenberg-Studer, E.M., Dobrynski, N., Sheldon, J., Schulz, T.F., Pechere, M., Nador, R.G., Spilliopoulos, A., Nicod, L., Saurat, J.H. (1999) "Human herpesvirus 8 seropositive patient with skin and graft Kaposi's sarcoma after lung transplantation." J. Am. Acad. Dermatol. 40: 308 - 311

Calabrò, M.L., Fiore, J.R., Favero, A., Lepera, A., Saracino, A., Angarano, G., Schulz, T.F.Chieco-Bianchi, L. (1999) "Detection of human herpesvirus 8 in cervicovaginal secretions and seroprevalence in human immunodeficiency virus type 1 -seropositive and -seronegative women." J.Inf. Dis. 179: 1534 - 1537

Lyall, E.G.H., Patton, G.S., Sheldon, J., Stainsbury, C., Mullen, J., O'Shea, S., Smith, N.A., de Ruiter, A., McClure, M. O., Schulz, T.F.(1999) "No evidence for vertical transmission of human herpesvirus 8 from HIV infected mothers." Paed. Inf. Dis. 18:795-799

Cook, P.M., Whitby, D., Calabro, M.-L., Luppi, M., Kakoola, D.N., Hjalgrim, H., Ariyoshi, K., Ensoli, B., Davison, A.J., Schulz, T.F., and the International Collaborative Group. (1999) "Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa." AIDS 13: 1165 - 1176

Glenn, M., Rainbow, L., Aurade, F., Davsion, A., Schulz, T.F.(1999) "Identification of a multiply spliced gene of KSHV/HHV8 with similarities to the latent membrane proteins of EBV." J.Virol. 73: 6953 - 6963

Platt, G.M., Simpson, G.R., Mittnacht, S., Schulz, T.F.1999. "Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene."J. Virol. 73: 9789 - 9795.

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