Viruses are known to play an important role in many lymphoproliferative diseases in animal models. The role of viruses as pathogenetic agents in human malignant lymphoma and leukemia is less clear. Epstein-Barr virus (EBV) plays an important role in some human cancers such as Burkitts lymhoma and nasopharyngeal carcinoma. Recently, EBV has been identified as a possible co-factor in other diseases, such as Hodgkins disease, lymphomatoid granulomatosis, nasal angiocentric T/NK cell lymphoma, HIV-associated lymphoma, and post-transplant lymphoproliferative disease of both B and T cell derivation. We are studying the expression of EBV-associated genes in human lymphoproliferative disease, and the role of gene expression in the pathophysiology these disorders. We previously have identifed a profile of EBV-induced chemokines (mIg, IP-10) which appear to be involved in the pathogenesis of EBV-associated tissue necrosis. More recently, we have characterized chemokine expression associated with eosinophilia in cases of both EBV-positive and EBV-negative Hodgkins disease. We found that Hodgkin?s disease tissues generally express higher levels of IP- 10, Mig, RANTES, MIP-1a and eotaxin, but not MDC, than tissues from lymphoid hyperplasia. Within Hodgkin?s disease cases, a significant direct correlation was detected between evidence of EBV infection in the neoplastic cells and levels of expression of IP-10, Mig, RANTES and MIP 1a. Levels of eotaxin expression were similar in EBV-positive and negative Hodgkin?s tissues, and correlated directly with the extent of tissue eosinophilia. By immunohistochemistry, IP 10 and Mig proteins localized with similar patterns in the malignant Reed-Sternberg cells and their variants, and to some surrounding inflammatory cells. These results provide evidence of high level chemokine expression in Hodgkin?s disease tissues, and suggest that chemokines play an important role in the recruitment of inflammatory cell infiltrates into tissues involved by Hodgkin?s disease.HHV-8 is a related herpes group virus that has been implicated in the pathogenesis of Kaposis sarsoma, primary effusion lymphoma, and multicentric Castlemans disease. We encountered a rare case of an HHV-8 associated MCD, followed by the development of an HHV-8- positive pleural PEL and a gastric large cell lymphoma in a human immunodeficiency virus (HIV)-seronegative male patient. The lesions were negative for Epstein-Barr virus (EBV). The combination of these diverse HHV-8 associated lymphoproliferative disorders in a single patient afforded us the ability to study differential gene expression in these conditions. HHV-8 DNA was demonstrated by PCR in lymphoid tissues involved by MCD and PEL. By RT- PCR, HHV-8 related transcripts, including vG-coupled protein receptor, vbcl2, vcyclin D, vIL-6, vMIPI, and vMIPII, were detected in the PEL from the pleural cavity and the gastric lymphoma, whereas these transcripts, except for vIL-6, were not detected in a lymph node biopsy with MCD. Expression of hIL-10 was weak in the PEL from the pleural cavity and expression of hIL-6 was undetectable in all three lesions. These data suggest that vIL-6 may be integral to the pathogenesis of MCD, whereas, other viral transcripts which encode oncogene homologues are important for tumorigenicity of this virus. - herpesviruses, Epstein-Barr virus, HHV-8/KSHV, Epidemiology, - Human Tissues, Fluids, Cells, etc.
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