Targeting human herpesvirus-8 for treatment of Kaposi's sarcoma and primary effusion lymphoma.
OBJECTIVE
Human herpesvirus-8, also called the Kaposi's sarcoma herpesvirus, is present in all cases of Kaposi's sarcoma and primary effusion lymphoma and in some cases of multicentric Castleman's disease. This review discusses mechanisms by which human herpesvirus-8 contributes to tumorigenesis and how this knowledge can be used to target the virus for the treatment of these tumors.


RESULTS
Most primary effusion lymphomas and Kaposi's sarcoma tumor cells are latently infected with human herpesvirus-8 and hence resistant to antiherpesvirus drugs that are dependent on lytic replication. In contrast, many of the cells infected with human herpesvirus-8 in multicentric Castleman's disease support lytic replication, so that clinical improvement frequently occurs in response to treatment with antiherpesvirus drugs. The resistance of latently-infected tumor cells to antiherpesvirus drugs can be overcome by inducing human herpesvirus-8 to reenter the lytic cascade in the presence of antiherpesvirus drugs. This leads to apoptosis of virally infected cells without increasing production of infectious virus. Alternatively, the replication and maintenance of the human herpesvirus-8 episome during latency can be disrupted by glycyrrhizic acid or hydroxyurea so that the virus no longer contributes to tumorigenesis. Both the innate and acquired immune systems can also be augmented to help prevent or treat human herpesvirus-8-associated tumors.


CONCLUSIONS
Novel strategies targeting human herpesvirus-8, which is present in all cases of Kaposi's sarcoma and primary effusion lymphoma, provide opportunities for selectively killing tumor cells.
Klass
Carmen Manuela
CM
Winship Cancer Institute, Emory University, 1365-B Clifton Road NE, Atlanta, GA 30322, USA.
Offermann
Margaret K
MK
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D024882:Drug Resistance, Viral; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D008223:Lymphoma / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007166:Immunosuppressive Agents