PMID- 10574624
OWN - NLM
STAT- MEDLINE
DCOM- 19991221
LR  - 20161124
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 19
IP  - 11
DP  - 1999 Nov
TI  - 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.
PG  - 1305-16
AB  - 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.
FAU - D'Agostino, G
AU  - D'Agostino G
AD  - Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy.
FAU - Arico, E
AU  - Arico E
FAU - Santodonato, L
AU  - Santodonato L
FAU - Venditti, M
AU  - Venditti M
FAU - Sestili, P
AU  - Sestili P
FAU - Masuelli, L
AU  - Masuelli L
FAU - Coletti, A
AU  - Coletti A
FAU - Modesti, A
AU  - Modesti A
FAU - Picchio, G
AU  - Picchio G
FAU - Mosier, D E
AU  - Mosier DE
FAU - Ferrantini, M
AU  - Ferrantini M
FAU - Belardelli, F
AU  - Belardelli F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 56588OP40D (interferon alfacon-1)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cell Division/physiology
MH  - Cell Line
MH  - Cell Transplantation
MH  - *Gene Transfer Techniques
MH  - HeLa Cells
MH  - *Herpesvirus 8, Human
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Interferon Type I/*genetics
MH  - Interferon-alpha
MH  - Lysogeny
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Recombinant Proteins
MH  - Sarcoma, Kaposi/*therapy
MH  - Severe Combined Immunodeficiency/*physiopathology
MH  - Virus Replication
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - 10.1089/107999099312984 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 1999 Nov;19(11):1305-16. doi: 10.1089/107999099312984.