Mechanisms for the inhibition of HIV replication by interferons-alpha, -beta, and -gamma in primary human macrophages

Details

Serval ID
serval:BIB_C929C9FA7201
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mechanisms for the inhibition of HIV replication by interferons-alpha, -beta, and -gamma in primary human macrophages
Journal
Virology
Author(s)
Meylan  P. R., Guatelli  J. C., Munis  J. R., Richman  D. D., Kornbluth  R. S.
ISSN
0042-6822 (Print)
Publication state
Published
Issued date
03/1993
Volume
193
Number
1
Pages
138-48
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S. --- Old month value: Mar
Abstract
Interferons (IFNs) inhibit the replication of a wide range of animal viruses by acting at various steps of the life cycle. Interferons display a particularly potent antiviral effect on HIV-1 replication in primary human macrophages. A high virus-to-cell multiplicity of infection was used to investigate which steps in a single replicative cycle in these primary human cells were affected by IFNs. Monocyte-derived macrophages from healthy seronegative donors were infected with HIV-1BaL. Virus production was assessed by immunoassay for p24 antigen. Viral DNA was detected by PCR while mRNA was detected specifically by RT-PCR with primers bracketing the 5' introns of HIV-1 to detect only spliced transcripts such as tat, rev, nef, and env mRNAs. Macrophages pretreated with IFN-alpha, -beta or -gamma had a reduced viral DNA signal while the spliced mRNA signal was essentially abolished. No virus was produced. To test whether IFNs could reduce HIV transcripts in cells with established productive infection, macrophages were infected and reinfection was then prevented by azidothymidine before starting interferon treatment. Under such conditions, the addition of interferons did not affect significantly the levels of HIV spliced transcripts. No intracellular accumulation of p24 antigen was observed. Therefore, the major effect of IFNs was at an early step of the virus life cycle and resulted in a reduced viral DNA synthesis.
Keywords
Cells, Cultured DNA, Viral/genetics Genes, Viral/genetics HIV/*drug effects/genetics/physiology HIV Core Protein p24/analysis Humans Interferon Type II/pharmacology Interferon-alpha/pharmacology Interferon-beta/pharmacology Interferons/*pharmacology Macrophages/*microbiology Polymerase Chain Reaction RNA, Messenger/genetics RNA, Viral/genetics Virus Replication/*drug effects/physiology
Pubmed
Web of science
Create date
25/01/2008 14:33
Last modification date
20/08/2019 15:44
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