title: Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein.
abstract: 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.
authors.affiliation: Laboratory of Viral Diseases; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, MD USA.
authors.forename: Deboeeta
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Departiment of Microbiology and Immunology; Rosalind Franklin University of Medicine and Science; Chicago, IL USA.
authors.forename: Bala
authors.initials: B
authors.lastname: Chandran
authors.affiliation: Laboratory of Viral Diseases; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, MD USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Berger
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology*; D001483:Base Sequence; D002522:Chlorocebus aethiops; D004261:DNA Replication / Q000187:drug effects / Q000276:immunology; D004279:DNA, Viral / Q000276:immunology; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D000922:Immunotoxins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014709:Vero Cells; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D006023:Glycoproteins; D000922:Immunotoxins; C113454:K8.1 protein, Human herpesvirus 8; D011994:Recombinant Proteins; D014764:Viral Proteins