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Review
. 2001 Mar;65(1):131-50.
doi: 10.1128/MMBR.65.1.131-150.2001.

Molecular pathways in virus-induced cytokine production

T H Mogensen  1 , S R Paludan
Affiliations
Review

Molecular pathways in virus-induced cytokine production

T H Mogensen et al. Microbiol Mol Biol Rev. 2001 Mar.

Abstract

Virus infections induce a proinflammatory response including expression of cytokines and chemokines. The subsequent leukocyte recruitment and antiviral effector functions contribute to the first line of defense against viruses. The molecular virus-cell interactions initiating these events have been studied intensively, and it appears that viral surface glycoproteins, double-stranded RNA, and intracellular viral proteins all have the capacity to activate signal transduction pathways leading to the expression of cytokines and chemokines. The signaling pathways activated by viral infections include the major proinflammatory pathways, with the transcription factor NF-kappaB having received special attention. These transcription factors in turn promote the expression of specific inducible host proteins and participate in the expression of some viral genes. Here we review the current knowledge of virus-induced signal transduction by seven human pathogenic viruses and the most widely used experimental models for viral infections. The molecular mechanisms of virus-induced expression of cytokines and chemokines is also analyzed.

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Figures

FIG. 1
FIG. 1
Principles in the activation of cellular signal transduction and gene expression by viruses. (A) Interaction of viral surface proteins with cellular receptors activates intracellular signaling. (B) Virion proteins released into the cytoplasm immediately after infection interact with cellular proteins. (C and D) Production of viral RNA and accumulation of large amounts of viral proteins induces stress signaling in infected cells. (E) Viral proteins produced during viral latency or the productive life cycle stimulate cellular signal transduction and gene expression.
FIG. 2
FIG. 2
Major cellular signaling pathways activated by viral infections. Virus-induced expression of cytokines and chemokines is primarily due to stimulation of one or more of the depicted signal transduction cascades, leading to activation of the following transcription factors: IRF-3 and IRF-7 (A), ATF-2/Jun (B), AP-1 (C), NF-AT (D), and NF-κB (E). For more detailed descriptions, see the text. S/T, serine/threonine.
FIG. 3
FIG. 3
Mechanisms of NF-κB activation by viruses. (A) Viral envelope glycoproteins activate signaling through engagement of cellular receptors. (B) Virus-encoded proteins interact with cellular signaling pathways and activate NF-κB. (C) Accumulation of dsRNA activates PKR, which in turn stimulates NF-κB activity. (D) ER overload due to massive viral protein expression can lead to activation of NF-κB.
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