RNA Viruses Triggered Signal Pathway

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RNA Viruses Triggered Signal Pathway
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• Part IViruses and Diseases

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Viruses and Diseases
RNA viruses
Viruses
Influenza virus
Hepatitis C virus (HCV)
SARS-CoV
Poliovirus
Influenza
Hepatitis C
SARS

• RNA viruses
• DNA viruses
• Retroviruses

Polio
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• Part IIResistance of Virus Infection

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How to Resist Virus Infection?

• Innate Immunity

Interferons Inflammatory cytokines

• Adaptive Immunity

Antibodies
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• Part IIIVirus Recognition

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Virus Recognition in Innate Immunity
DNA viruses are recognized by cGAS and TLR9
cGAS
TLR9
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Virus Recognition in Innate Immunity
RNA viruses are recognized by RLRs

• RLRs structure contains
• One C-terminal regulatory domain (RD)
• One central DEAD box helicase/ATPase domain
  (DExD/H helicase domain)
• Two N-terminal caspase recruitment domains (CARDs)

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Structure of RLRs
Differences between RIG-I, MDA5 and LGP2
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Recognition of RNA Viruses
RIG-I and MDA5 recognize different kind of RNA
viruses

• RIG-I recognize
• Sendai virus (SeV)
• vesicular stomatitis virus (VSV)
• Japanese encephalitis virus (JEV)
• Newcastle disease virus (NDV)
• Influenza virus
• Hepatitis C virus (HCV)

• MDA5 recognize
• Mengo virus
• Theilers virus
• Encephalomyocarditis virus (EMCV)

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RIG-I Recognize Short dsRNAs

• Short dsRNA (up to 1 kb) is recognized by RIG-I.
• Type I IFN-inducing activity is greatly enhanced
  by the presence of its 5triphosphate.
• The activation of RIG-I needs double-stranded RNA.

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MDA5 Recognize Long dsRNAs

• MDA5 detects long dsRNA (more than 2 kb) like
  poly IC.
• MDA5-/-mice show stongly reduced production of
  type I IFNs but not IL-12 in response to poly IC
  stimulation in vivo.

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LGP2 Regulate Virus Recognition

• LGP2 lacks a CARD domain.
• In vitro studies suggested that LGP2 is a
  negative regulator of RIG-I and MDA5 signaling.
• In vivo studies indicated that LGP2 positively
  regulates both RIG-I and MDA5 mediated production
  of type I IFNs.
• LGP2 is dispensable for type I IFN production.

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• Part IVCritical Adaptor MAVS

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Critical Adaptor MAVS (IPS-1)
MAVS mitochondrial antiviral-signaling protein,
is also named VISA, IPS-1 and Cardif.
STRUCTURE A N-terminal CARD domain, A
proline-rich (PRO) region A C-terminal
transmembrane (TM) region.

• The CARD domain and the TM domain are essential
  for the function of MAVS.
• MAVS CARD domain is not sufficient to induce
  IFN-ß.

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Critical Adaptor MAVS (IPS-1)

• MAVS (IPS-1) is located on the mitochondrial
  membrane.
• The CARD-domain interacts with CARDs of RLRs for
  triggering signaling axis.

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• Part VTwo Downstream Signal Axis

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Two Downstream Signal Axis of MAVS

1. Type I IFNs production axis.
2. Cytokines production axis.

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Type I IFNs Production Axis
TBK1 dimerization
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Cytokines Production Axis
TRADD and FADD transmit signal resulting in the
Cleavage of caspase-8/-10. This process activates
NF-?B to induce cytokines production.
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• Part VISummary

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Summary of RNA Viruses Triggered Signaling
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