期刊
MABS
卷 4, 期 2, 页码 233-242出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/mabs.4.2.19262
关键词
targeted cytotoxic proteins; human herpesvirus-8; KSHV surface glycoprotein; KSHV lytic infection; multicentric Castleman disease; pseudomonas exotoxin A; ganciclovir; reciprocal drug potentiation
资金
- NIH, NIAID
Kaposi sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is etiologically associated with three neoplastic syndromes: Kaposi sarcoma and the uncommon HIV-associated B-cell lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman disease. The incidence of the latter B-cell pathology has been increasing in spite of antiretroviral therapy; its association with lytic virus replication has prompted interest in therapeutic strategies aimed at this phase of the virus life cycle. We designed and expressed a recombinant immunotoxin (2014-PE38) targeting the gpK8.1A viral glycoprotein expressed on the surface of the virion and infected cells. We show that this immunotoxin selectively kills KSHV-infected cells in dose-dependent fashion, resulting in major reductions of infectious virus release. The immunotoxin and ganciclovir, an inhibitor of viral DNA replication, showed marked reciprocal potentiation of antiviral activities. These results suggest that the immunotoxin, alone or in combination, may represent a new approach to treat diseases associated with KSHV lytic replication.
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