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https://hdl.handle.net/2440/44186
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Type: | Journal article |
Title: | Dengue virus (DV) replication in monocyte-derived macrophages is not affected by tumor necrosis factor alpha (TNF-alpha), and DV infection induces altered responsiveness to TNF-alpha stimulation |
Author: | Wati, S. Li, P. Burrell, C. Carr, J. |
Citation: | Journal of Virology, 2007; 81(18):10161-10171 |
Publisher: | Amer Soc Microbiology |
Issue Date: | 2007 |
ISSN: | 0022-538X 1098-5514 |
Statement of Responsibility: | Satiya Wati, Peng Li, Christopher J. Burrell, and Jillian M. Carr |
Abstract: | Tumor necrosis factor alpha (TNF-alpha) is believed to play a significant role in the pathogenesis of dengue virus (DV) infection, with elevated levels of TNF-alpha in the sera of DV-infected patients paralleling the severity of disease and TNF-alpha release being coincident with the peak of DV production from infected monocyte-derived macrophages (MDM) in vitro. Since macrophages are a primary cell target in vivo for DV infection, we investigated the potential antiviral role of TNF-alpha in regulating DV replication in MDM. While pretreatment of MDM with TNF-alpha had a minor inhibitory effect, addition of TNF-alpha to MDM with established DV infection had no effect on DV replication as measured by DV RNA levels or progeny virus production. Blocking endogenous TNF-alpha using short interfering RNA or inhibitory TNF-alpha antibodies also had no effect on infectious DV production or viral RNA synthesis. Together, these results demonstrate that DV replication in MDM is not affected by TNF-alpha. Additionally, normal cellular TNF-alpha signaling, measured by quantitation of TNF-alpha-induced stimulation of transcription from an NF-kappaB-responsive reporter plasmid or NF-kappaB protein nuclear translocation, was blocked in DV-infected MDM and Huh7 cells. Thus, DV replication in MDM is not affected by TNF-alpha, and infected cells do not respond normally to TNF-alpha stimulation. It is therefore unlikely that the increased production of TNF-alpha seen in DV infection directly effects DV clearance by reducing DV replication, and the ability of DV to alter TNF-alpha responsiveness highlights another example of viral subversion of cellular functions. |
Keywords: | Vero Cells Cell Nucleus Macrophages Animals Humans Mice Dengue Virus Dengue Tumor Necrosis Factor-alpha NF-kappa B RNA, Small Interfering RNA, Viral Antibodies Virus Replication Signal Transduction Active Transport, Cell Nucleus Chlorocebus aethiops |
Description: | Copyright © 2007, American Society for Microbiology. All Rights Reserved. |
DOI: | 10.1128/JVI.00313-07 |
Published version: | http://jvi.asm.org/cgi/content/abstract/81/18/10161 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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