The 3′ CCACCA Sequence of tRNA
            <sup>Ala</sup>
            (UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3

Wang, Zhijun; Li, Xiang; Shao, Junjie; Yuan, Zhenghong

doi:10.1128/cvi.00019-06

Cited by 27 publications

(26 citation statements)

References 40 publications

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“…The virus-associated dsRNA involved in APR induction by influenza virus could come from several sources, including viral replication intermediates (Majde, 2000), small interfering RNAs (Kariko et al, 2004a), t-RNAs (Wang et al, 2006) and certain forms of host mRNA from dead cells (Kariko et al, 2004b)]. All of these sources could be recognized by intracellular TLR3 (see below) or released into the extracellular environment when influenza-infected cells die (Majde et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

Majde

Kapás

Bohnet

et al. 2010

Brain, Behavior, and Immunity

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Certain sickness behaviors occur consistently in influenza-infected humans and mice. These include body temperature changes, somnolence, and anorexia. Several cytokines serve as mediators of the influenza acute phase response (APR), including these sickness behaviors, and one likely inducer of these cytokines is dsRNA produced during viral replication. TLR3 is known to be one of the host cellular components capable of recognizing dsRNA and activating cytokine synthesis. To determine the role of TLR3-detected viral dsRNA in the causation of viral symptoms, TLR3-deficient mice (TLR3 knockouts, or KOs) were infected with a marginally lethal dose of mouse-adapted X-31 influenza virus. TLR3 KOs and their wild-type (WT) controls were monitored for baseline body temperature, locomotor activity, and sleep profiles prior to infection. Both mouse strains were then infected and monitored for changes in these sickness behaviors plus body weight changes and mortality for up to 14 days post-infection. Consistent with the observations that influenza pathology is reduced in TLR3 KOs, we showed that hypothermia after post-infection day 5 and the total loss of body weight were attenuated in the TLR3 KOs. Sleep changes characteristic of this infection model [particularly increased non-rapid-eye-movement sleep (NREMS)] were also attenuated in TLR3 KOs and returned to baseline values more rapidly. Locomotor activity suppression was similar in both strains. Therefore virus-associated dsRNA detected by TLR3 appears to play a substantial role in mediating several aspects of the influenza syndrome in mice.

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Section: Discussionmentioning

confidence: 99%

Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

Majde

Kapás

Bohnet

et al. 2010

Brain, Behavior, and Immunity

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“…For example, tRNA may act as a primer in DNA synthesis (Marquet et al, 1995), and a role for tRNA in the regulation of ColE1 plasmid DNA replication in amino-acid-starved E. coli has been proposed (Wró bel & Wqgrzyn, 1997, 1998Wqgrzyn, 1999;Wang et al, 2002). Recently, it was also demonstrated that tRNA can be used as a kind of T helper 1 immune adjuvant (Wang et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

tRNA-dependent cleavage of the ColE1 plasmid-encoded RNA I

Wang

Yuan

et al. 2006

Microbiology

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Effects of tRNA Ala (UGC) and its derivative devoid of the 39-ACCA motif [tRNA Ala (UGC)DACCA] on the cleavage of the ColE1-like plasmid-derived RNA I were analysed in vivo and in vitro. In an aminoacid-starved relA mutant, in which uncharged tRNAs occur in large amounts, three products of specific cleavage of RNA I were observed, in contrast to an otherwise isogenic relA + host. Overexpression of tRNA Ala (UGC), which under such conditions occurs in Escherichia coli mostly in an uncharged form, induced RNA I cleavage and resulted in an increase in ColE1-like plasmid DNA copy number. Such effects were not observed during overexpression of the 39-ACCA-truncated tRNA Ala (UGC). Moreover, tRNA Ala (UGC), but not tRNA Ala (UGC)DACCA, caused RNA I cleavage in vitro in the presence of MgCl 2 . These results strongly suggest that tRNA-dependent RNA I cleavage occurs in ColE1-like plasmid-bearing E. coli, and demonstrate that tRNA Ala (UGC) participates in specific degradation of RNA I in vivo and in vitro. This reaction is dependent on the presence of the 39-ACCA motif of tRNA Ala (UGC).

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“…The potential involvement of TLR3 may help account for the prominence of antiribonucleoprotein responses observed in autoimmune diseases (42). Additionally, a specific motif of the endogenous tRNA(Ala)(UGC) that induces TH1 and cytotoxic-T-lymphocyte immune responses was shown to be effectively recognized by TLR3 (107). In addition to nucleoside modification and the endosomal localization of TLR3, glycosylation of the TLR3 extracellular domain might provide a mechanism for discriminating between host and foreign RNA.…”

Section: Tlr3 Structure Ligand Binding and Specificitymentioning

confidence: 99%

Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3

2008

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SUMMARY Toll-like receptors (TLRs) form a major group of transmembrane receptors that are involved in the detection of invading pathogens. Double-stranded RNA is a marker for viral infection that is recognized by TLR3. TLR3 triggering activates specific signaling pathways that culminate in the activation of NF-κB and IRF3 transcription factors, as well as apoptosis, enabling the host to mount an effective innate immune response through the induction of cytokines, chemokines, and other proinflammatory mediators. In this review, we describe the paradoxical role of TLR3 in innate immunity against different viruses and in viral pathogenesis but also the evidence for TLR3 as a “danger” receptor in nonviral diseases. We also discuss the structure and cellular localization of TLR3, as well as the complex signaling and regulatory events that contribute to TLR3-mediated immune responses.

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The 3′ CCACCA Sequence of tRNA ^Ala (UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3

Cited by 27 publications

References 40 publications

Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

tRNA-dependent cleavage of the ColE1 plasmid-encoded RNA I

Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3

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The 3′ CCACCA Sequence of tRNA Ala (UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3

Cited by 27 publications

References 40 publications

Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

Attenuation of the influenza virus sickness behavior in mice deficient in Toll-like receptor 3

tRNA-dependent cleavage of the ColE1 plasmid-encoded RNA I

Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3

Contact Info

Product

Resources

About

The 3′ CCACCA Sequence of tRNA ^Ala (UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3