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PMID: 10196299 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alpha interferon inhibits human herpesvirus 8 (HHV-8) reactivation in primary effusion lymphoma cells and reduces HHV-8 load in cultured peripheral blood mononuclear cells.

Journal of virology ·Vol. 73 ·No. 5 ·1999-05-00 ·Pages 4029-41

Monini P, Carlini F, Stürzl M, Rimessi P, Superti F, Franco M, Melucci-Vigo G, Cafaro A, Goletti D, Sgadari C, Butto' S, Leone P, Chiozzini C, Barresi C, Tinari A, Bonaccorsi A, Capobianchi MR, Giuliani M, di Carlo A, Andreoni M, Rezza G, Ensoli B

Abstract

Infection by human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma (KS). Since regression of KS can be achieved by treatment of the patients with alpha interferon (IFN-alpha), we analyzed the effects of IFN-alpha or anti-IFN-alpha antibodies (Ab) on HHV-8 latently infected primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-alpha inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1 and kaposin genes that are induced early and several hours, respectively, after TPA treatment. In addition, IFN-alpha inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-1 and kaposin genes by IFN-alpha was also observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti-IFN-alpha Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature enveloped particles and in a more extensive cytopathic effect due to the neutralization of the endogenous IFN produced by these cells. IFN was also produced by cultured PBMC from HHV-8-infected individuals, and this was associated with a loss of viral DNA during culture. However, the addition of anti-IFN-alpha Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA in these cells that was associated with the detection of the latency-associated kaposin RNA. Finally, the addition of IFN-alpha reduced the HHV-8 load in PBMC. Thus, IFN-alpha appears to have inhibitory effects on HHV-8 persistent infection of PBMC. These results suggest that, in addition to inhibiting the expression of angiogenic factors that are key to KS development, IFN-alpha may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation.

MeSH Terms
Genes, Viral Herpesvirus 8, Human/growth & development,immunology Humans Interferon alpha-2 Interferon-alpha/immunology,pharmacology Leukocytes, Mononuclear/virology Lymphoma Male Morphogenesis Recombinant Proteins Tetradecanoylphorbol Acetate/pharmacology Tumor Cells, Cultured Viral Load Virion Virus Activation
Chemicals
Interferon alpha-2 Interferon-alpha Recombinant Proteins Tetradecanoylphorbol Acetate
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Monini P
Laboratory of Virology, Institute of Virology, University "La Sapienza".
Carlini F
Stürzl M
Rimessi P
Superti F
Franco M
Melucci-Vigo G
Cafaro A
Goletti D
Sgadari C
Butto' S
Leone P
Chiozzini C
Barresi C
Tinari A
Bonaccorsi A
Capobianchi M R
Giuliani M
di Carlo A
Andreoni M
Rezza G
Ensoli B
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.5.4029-4041.1999
Published
1999-05-00
Pages
4029-41
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC104182
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.73.5.4029-4041.1999 PMC Full Text View journal details
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