Brian J Nickoloff1, Kimberly E Foreman. 1. Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA.
Abstract
OBJECTIVE: To provide an overview of the role for HHV-8 as the causative agent responsible for Kaposi's sarcoma, the molecular cross-talk between HHV-8 and HIV-1, and the ability of specific cytokines to influence the pathophysiology of this malignancy. PATIENTS: Normal human skin grafts were studied using a SCID mouse xenograft model system in which engrafted skin was injected intradermally with HHV-8 and/or HIV-1, and the subsequent induction of clinical, histologic, and viral titer changes were assessed in serial fashion. RESULTS: Following intradermal injection of HHV-8 into engrafted normal human skin, cutaneous lesions resembling Kaposi's sarcoma were created in numerous different grafts. These lesions were characterized by routine light microscopy as well as by immunophenotypic and molecular virological assessments. As several grafts injected with HHV-8 failed to develop Kaposi's sarcoma, we sought to determine whether another cofactor was required and this led us to uncover the ability of HHV-8 and HIV-1 to reciprocally influence each other using both in vitro and in vivo studies. Given the importance of various cytokines, the influence of scatter factor and IFN-gamma in the pathophysiology of Kaposi's sarcoma was also evaluated. CONCLUSION: Based on these in vivo studies using SCID mice engrafted with human skin and injected with HHV-8, we conclude that HHV-8 is the etiologic agent in Kaposi's sarcoma, and that HIV-1 and HHV-8 can influence each other involving both direct and indirect cross-talk mechanisms.
OBJECTIVE: To provide an overview of the role for HHV-8 as the causative agent responsible for Kaposi's sarcoma, the molecular cross-talk between HHV-8 and HIV-1, and the ability of specific cytokines to influence the pathophysiology of this malignancy. PATIENTS: Normal human skin grafts were studied using a SCIDmouse xenograft model system in which engrafted skin was injected intradermally with HHV-8 and/or HIV-1, and the subsequent induction of clinical, histologic, and viral titer changes were assessed in serial fashion. RESULTS: Following intradermal injection of HHV-8 into engrafted normal human skin, cutaneous lesions resembling Kaposi's sarcoma were created in numerous different grafts. These lesions were characterized by routine light microscopy as well as by immunophenotypic and molecular virological assessments. As several grafts injected with HHV-8 failed to develop Kaposi's sarcoma, we sought to determine whether another cofactor was required and this led us to uncover the ability of HHV-8 and HIV-1 to reciprocally influence each other using both in vitro and in vivo studies. Given the importance of various cytokines, the influence of scatter factor and IFN-gamma in the pathophysiology of Kaposi's sarcoma was also evaluated. CONCLUSION: Based on these in vivo studies using SCIDmice engrafted with human skin and injected with HHV-8, we conclude that HHV-8 is the etiologic agent in Kaposi's sarcoma, and that HIV-1 and HHV-8 can influence each other involving both direct and indirect cross-talk mechanisms.
Authors: Masatoshi Deguchi; Diana Whitaker-Menezes; Stephen C Jones; Setsuya Aiba; Satoshi Nakagawa; Hachiro Tagami; Robert Korngold; George F Murphy Journal: Am J Pathol Date: 2003-11 Impact factor: 4.307
Authors: Elisabeth A Seftor; P S Meltzer; D A Kirschmann; N V Margaryan; R E B Seftor; Mary J C Hendrix Journal: J Cell Mol Med Date: 2006 Jan-Mar Impact factor: 5.310