Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-12-21
pubmed:abstractText
In this study, we investigated the effects of human type I consensus interferon (IFN-con1) (Amgen) gene transfer into body cavity-based lymphomas (BCBL)-1 cells, which are latently infected with Kaposi's sarcoma-associated herpesvirus (KSHV) human herpesvirus-8 (HHV-8). Both the basal and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated production of KSHV/HHV-8 mature virions was strongly inhibited in genetically modified IFN-producing BCBL-1 cells as compared with parental or control transduced counterparts. A similar inhibition was obtained on treatment of parental BCBL-1 cells with exogenous IFN-con1. The reduction in KSHV/HHV-8 production was associated with a decrease in the basal and TPA-stimulated intracellular amount of the linear form of the viral genome. Interestingly, 25%40% of the IFN-producing BCBL-1 cell population underwent spontaneous apoptosis in vitro. TPA treatment, which did not significantly affect the viability of the parental and control BCBL-1 cells, resulted in the apoptotic death of up to 70% of the IFN-producing cell population. Addition of exogenous IFN-con1 to parental BCBL-1 cells produced similar effects, although less intense. Injection of either parental or control-transduced BCBL-1 cells into SCID mice resulted in progressively growing tumors characterized by an unusually high level of tumor angiogenesis. In contrast, complete tumor regression was observed in all the mice injected either subcutaneously (s.c.) or intraperitoneally (i.p.) with the IFN-producing BCBL-1 cells. These results represent the first evidence that type I IFN can counteract the activation of a productive herpesvirus infection in latently infected tumor cells by the induction of apoptosis, providing an interesting link between the antiviral and antitumor activities of this cytokine. These data suggest the possible advantages of strategies of type I IFN gene transfer (with respect to the use of the exogenous cytokine) for the treatment of patients with some HHV-8-induced malignancies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1079-9907
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1305-16
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10574624-Animals, pubmed-meshheading:10574624-Apoptosis, pubmed-meshheading:10574624-Cell Division, pubmed-meshheading:10574624-Cell Line, pubmed-meshheading:10574624-Cell Transplantation, pubmed-meshheading:10574624-Gene Transfer Techniques, pubmed-meshheading:10574624-HeLa Cells, pubmed-meshheading:10574624-Herpesvirus 8, Human, pubmed-meshheading:10574624-Humans, pubmed-meshheading:10574624-In Situ Nick-End Labeling, pubmed-meshheading:10574624-Interferon Type I, pubmed-meshheading:10574624-Interferon-alpha, pubmed-meshheading:10574624-Lysogeny, pubmed-meshheading:10574624-Male, pubmed-meshheading:10574624-Mice, pubmed-meshheading:10574624-Mice, SCID, pubmed-meshheading:10574624-Recombinant Proteins, pubmed-meshheading:10574624-Sarcoma, Kaposi, pubmed-meshheading:10574624-Severe Combined Immunodeficiency, pubmed-meshheading:10574624-Virus Replication
pubmed:year
1999
pubmed:articleTitle
Type I consensus IFN (IFN-con1) gene transfer into KSHV/HHV-8-infected BCBL-1 cells causes inhibition of viral lytic cycle activation via induction of apoptosis and abrogates tumorigenicity in sCID mice.
pubmed:affiliation
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't