Modulation of Dengue virus infection in human cells by alpha, beta, and gamma interferons.
A role for interferon (IFN) in modulating infection by dengue virus (DV) has been suggested by studies in DV-infected patients and IFN receptor-deficient mice. To address how IFN modulates DV type 2 infection, we have assayed IFN-alpha, -beta, and -gamma for the ability to enhance or diminish antibody-independent and antibody-dependent cell infection using a competitive, asymmetric reverse transcriptase-mediated PCR (RT-PCR) assay that quantitates positive and negative strands of viral RNA, a flow cytometric assay that measures viral antigen, and a plaque assay that analyzes virion production. Our data suggest that IFN-alpha and -beta protect cells against DV infection in vitro. Treatment of hepatoma cells with IFN-alpha or -beta decreases viral RNA levels greater than 1, 000-fold, the percentage of cells infected 90 to 95%, and the amount of infectious virus secreted 150- to 100,000-fold. These results have been reproduced with several cell types and viral strains, including low-passage isolates. In contrast, IFN-gamma has a more variable effect depending on the cell type and pathway of infection. Quantitative RT-PCR experiments indicate that IFN inhibits DV infection by preventing the accumulation of negative-strand viral RNA.
Diamond
M S
MS
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, California 94720, USA.
Roberts
T G
TG
Edgil
D
D
Lu
B
B
Ernst
J
J
Harris
E
E
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003716:Dengue Virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D020014:K562 Cells; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000914:Antibodies, Viral; D000998:Antiviral Agents; D016898:Interferon-alpha; D016899:Interferon-beta; D007371:Interferon-gamma