Next Article in Journal
The Future of HCV Therapy: NS4B as an Antiviral Target
Next Article in Special Issue
Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses
Previous Article in Journal
Making of Viral Replication Organelles by Remodeling Interior Membranes
Previous Article in Special Issue
Avian Bornaviruses Escape Recognition by the Innate Immune System
Viruses 2010, 2(11), 2443-2480; doi:10.3390/v2112443
Review

Inhibition of the Type I Interferon Antiviral Response During Arenavirus Infection

1
, 2,*  and 3,*
Received: 8 October 2010; in revised form: 22 October 2010 / Accepted: 22 October 2010 / Published: 5 November 2010
(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)
Download PDF [267 KB, uploaded 5 November 2010]
Abstract: Arenaviruses merit interest both as tractable experimental model systems to study acute and persistent viral infections, and as clinically-important human pathogens. Several arenaviruses cause hemorrhagic fever (HF) disease in humans. In addition, evidence indicates that the globally-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a human pathogen of clinical significance in congenital infections, and also poses a great danger to immunosuppressed individuals. Arenavirus persistence and pathogenesis are facilitated by their ability to overcome the host innate immune response. Mammalian hosts have developed both membrane toll-like receptors (TLR) and cytoplasmic pattern recognition receptors (PRRs) that recognize specific pathogen-associated molecular patterns (PAMPs), resulting in activation of the transcription factors IRF3 or IRF7, or both, which together with NF-κB and ATF-2/c-JUN induce production of type I interferon (IFN-I). IFN-I plays a key role in host anti-microbial defense by mediating direct antiviral effects via up-regulation of IFN-I stimulated genes (ISGs), activating dendritic cells (DCs) and natural killer (NK) cells, and promoting the induction of adaptive responses. Accordingly, viruses have developed a plethora of strategies to disrupt the IFN-I mediated antiviral defenses of the host, and the viral gene products responsible for these disruptions are often major virulence determinants.IRF3- and IRF7-dependent induction of host innate immune responses is frequently targeted by viruses. Thus, the arenavirus nucleoprotein (NP) was shown to inhibit the IFN‑I response by interfering with the activation of IRF3. This NP anti-IFN activity, together with alterations in the number and function of DCs observed in mice chronically infected with LCMV, likely play an important role in LCMV persistence in its murine host. In this review we will discuss current knowledge about the cellular and molecular mechanisms by which arenaviruses can subvert the host innate immune response and their implications for understanding HF arenaviral disease as well as arenavirus persistence in their natural hosts.
Keywords: arenavirus; type I interferon; hemorrhagic fever; innate immunity; lymphocytic choriomeningitis virus; nucleoprotein; dendritic cells arenavirus; type I interferon; hemorrhagic fever; innate immunity; lymphocytic choriomeningitis virus; nucleoprotein; dendritic cells
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Borrow, P.; Martínez-Sobrido, L.; De la Torre, J.C. Inhibition of the Type I Interferon Antiviral Response During Arenavirus Infection. Viruses 2010, 2, 2443-2480.

AMA Style

Borrow P, Martínez-Sobrido L, De la Torre JC. Inhibition of the Type I Interferon Antiviral Response During Arenavirus Infection. Viruses. 2010; 2(11):2443-2480.

Chicago/Turabian Style

Borrow, Persephone; Martínez-Sobrido, Luis; De la Torre, Juan C. 2010. "Inhibition of the Type I Interferon Antiviral Response During Arenavirus Infection." Viruses 2, no. 11: 2443-2480.


Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert