Induction and Inhibition of Type I Interferon Responses by Distinct Components of Lymphocytic Choriomeningitis Virus

Zhou, Sasha; Cerny, Anna M.; Zacharia, An; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; Finberg, Robert W.

doi:10.1128/jvi.00155-10

Cited by 114 publications

(142 citation statements)

References 68 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…Finally, in contrast to our investigations using defined RNAs based on the known structures of arenavirus genomes, two other groups have extracted the RNAs from polyethylene glycol precipitates of the supernatants of lassa virus and lymphocytic choriomeningitis virus-infected cultures, and both have found that these RNAs induce IFN when transfected into cells (30,31). However, given that arenavirions are known to include cellular components like ribosomes, they may therefore also contain some antigenome segments and mRNAs as well.…”

Section: Discussionmentioning

confidence: 82%

Short Double-stranded RNAs with an Overhanging 5′ ppp-Nucleotide, as Found in Arenavirus Genomes, Act as RIG-I Decoys

Marq

Hausmann

Veillard

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Arenavirus RNA genomes are initiated by a "prime and realign" mechanism, such that the initiating GTP is found as a single unpaired (overhanging) nucleotide when the complementary genome ends anneal to form double-stranded (ds) RNA panhandle structures. dsRNAs modeled on these structures do not induce interferon (IFN), as opposed to bluntended 5 ppp dsRNA. This study examines whether these viral structures can also act as decoys, by trapping RIG-I in inactive dsRNA complexes. We examined the ability of various dsRNAs to activate the RIG-I ATPase (presumably a measure of helicase translocation on dsRNA) relative to their ability to induce IFN. We found that there is no simple relationship between these two properties, as if RIG-I can translocate on short dsRNAs without inducing IFN. Moreover, we found that 5 ppp dsRNAs with a single unpaired 5 ppp-nucleotide can in fact competitively inhibit the ability of blunt-ended 5 ppp dsRNAs to induce IFN when co-transfected into cells and that this inhibition is strongly dependent on the presence of the 5 ppp. In contrast, 5 ppp dsRNAs with a single unpaired 5 ppp-nucleotide does not inhibit poly(I-C)-induced IFN activation, which is independent of the presence of a 5 ppp group.

show abstract

Section: Discussionmentioning

confidence: 82%

Short Double-stranded RNAs with an Overhanging 5′ ppp-Nucleotide, as Found in Arenavirus Genomes, Act as RIG-I Decoys

Marq

Hausmann

Veillard

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Previous studies in C57BL/6 mice showed that induction of these cytokines by LCMV is mediated by viral RNA engagement of both endosomal Toll-like receptors (TLRs) and cytosolic RNA sensors (RIG-I and MDA5) (28)(29)(30)(31)(32). We found that congenic NZB mice lacking either expression of TLR3 (Tlr3 −/− ), or signaling by all endosomal TLRs (TLRs 3, 7, and 9) due to the 3d mutation of UNC93B1 (Unc93b1 3d/3d ) (33), succumbed to Cl13 infection unless treated with IFNAR-blocking antibody (Fig.…”

Section: Cl13 Induces In Nzb Mice a Pathogenic Cytotoxic T-cell Responsementioning

confidence: 99%

Type I interferon is a therapeutic target for virus-induced lethal vascular damage

Baccalà¹,

Welch²,

Gonzalez-Quintial³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Lassa virus is, after dengue virus, the second most common cause of viral hemorrhagic fever. In susceptible individuals, Lassa virus infection is associated with vascular permeability, leading to tissue edema, organ failure, and death. Hemorrhagic fever viruses efficiently infect vascular endothelial cells, but are generally considered noncytopathic. Thus, the mechanism of virus-induced vascular injury remains unclear. Using the lymphocytic choriomeningitis virus variant clone 13, a prototype of Lassa virus, we show here that lethal vascular leakage in susceptible mice was completely prevented by type I IFN receptor blockade. Therefore, approaches that target type I IFNs or effector molecules induced by these cytokines may be considered for the treatment of Lassa fever and other severe hemorrhagic viral illnesses.

show abstract

“…LCMV NP blockade of the IRF-3 pathway also affects the response to RIG-I and MDA5 (Zhou et al 2010). Moreover, this same study demonstrated that LCMV NP physically interacts with both RIG-I and MDA5.…”

Section: Chronic Lcmv Infections Suppress Type I Interferon Expressionmentioning

confidence: 52%

“…Moreover, this same study demonstrated that LCMV NP physically interacts with both RIG-I and MDA5. Mutations in LCMV NP that prevented the inhibition of type I IFN however did not affect this interaction, which suggests that there are additional inhibitory mechanisms (Zhou et al 2010). …”

Section: Chronic Lcmv Infections Suppress Type I Interferon Expressionmentioning

confidence: 99%

“…High levels of type I IFN have been detected at early time points during an acute, LCMV Arm infection (Montoya, Edwards et al 2005). Zhou et al have demonstrated that this induction of type I IFN is due at least in part to the recognition of the LCMV RNA genome by retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) pathway along with toll-like receptor (TLR) 2 and 6 (Zhou, Kurt-Jones et al 2005;Zhou, Cerny et al 2010). Similarly, DCs from LCMV Cl 13-infected mice have also been shown to produce type I IFN at early time points of virus infection (Dalod, Salazar-Mather et al 2002;Diebold, Montoya et al 2003;Zuniga, Hahm et al 2007).…”

Section: Chronic Lcmv Infections Suppress Type I Interferon Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Viruses Strive to Suppress Host Immune Responses and Prolong Persistence

Pritzl¹,

Seo²,

Hahm³

2012

Recent Advances in Immunology to Target Cancer, Inflammation and Infections

View full text Add to dashboard Cite

Induction and Inhibition of Type I Interferon Responses by Distinct Components of Lymphocytic Choriomeningitis Virus

Cited by 114 publications

References 68 publications

Short Double-stranded RNAs with an Overhanging 5′ ppp-Nucleotide, as Found in Arenavirus Genomes, Act as RIG-I Decoys

Short Double-stranded RNAs with an Overhanging 5′ ppp-Nucleotide, as Found in Arenavirus Genomes, Act as RIG-I Decoys

Type I interferon is a therapeutic target for virus-induced lethal vascular damage

Viruses Strive to Suppress Host Immune Responses and Prolong Persistence

Contact Info

Product

Resources

About