Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model

Gerlier, Denis; Lyles, Douglas S.

doi:10.1128/mmbr.00007-11

Cited by 87 publications

(83 citation statements)

References 319 publications

(431 reference statements)

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“…Mononegavirales are nonsegmented negative-stranded RNA viruses that share a complex and unique mode of transcription and replication (1,2). Virions are enveloped, and the single strand of genomic RNA is encapsidated by the nucleoprotein (N).…”

Section: Measles Virus (Mev)mentioning

confidence: 99%

Plasticity in Structural and Functional Interactions between the Phosphoprotein and Nucleoprotein of Measles Virus

Shu

Habchi

Costanzo

et al. 2012

Journal of Biological Chemistry

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Background: Binding of the MeV C-terminal disordered domain of the nucleoprotein (N TAIL ) to the X domain (XD) of the phosphoprotein mediates recruitment of the polymerase. Results: N TAIL amino acid substitutions that reduce N TAIL -XD affinity and/or N TAIL ␣-helical folding do not affect polymerase rates but strongly affect infectivity. Conclusion: MeV polymerase tolerates N TAIL amino acid substitutions. Significance: N TAIL sequence plays a role in optimal infectivity.

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Section: Measles Virus (Mev)mentioning

confidence: 99%

Plasticity in Structural and Functional Interactions between the Phosphoprotein and Nucleoprotein of Measles Virus

Shu

Habchi

Costanzo

et al. 2012

Journal of Biological Chemistry

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“…Cytoplasmic viral RNA is detected by helicase receptors such as RIG-I. These receptors bind short RNA products, functionally couple with the mitochondrial antiviral signaling protein (MAVS), and activate downstream kinases and transcription factors, leading to interferon (IFN) production and upregulation of interferon-stimulated genes (11,12).…”

mentioning

confidence: 99%

The Interferon Type I/III Response to Respiratory Syncytial Virus Infection in Airway Epithelial Cells Can Be Attenuated or Amplified by Antiviral Treatment

McCutcheon

Jordan

Mawhorter

et al. 2016

J Virol

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Human respiratory syncytial virus (RSV) is a single-stranded RNA virus that causes acute, and occasionally fatal, lower respiratory illness in young infants, the elderly, and immunocompromised patients. Therapeutic interventions able to cut short viral replication and quickly return the airways to normal function are needed. An understanding of antiviral activities and their effects on host defense mechanisms is important for the design of safe and effective therapy. We targeted functionally and temporally distinct steps within the viral life cycle using small-molecule RSV inhibitors and studied their antiviral activities and their effects on innate interferon responses of airway epithelial cells in vitro. H uman respiratory syncytial virus (RSV) is a single-stranded, negative-sense RNA virus belonging to the family Paramyxoviridae. Premature and very young infants are at the highest risk of having severe lower respiratory tract infections and, later, a higher incidence of chronic asthma (1). Older adults with chronic lung or heart disease and individuals with suppressed immune systems also often require medical care after RSV infection. The lack of long-lasting protection after primary infection contributes to the capacity of RSV to cause yearly outbreaks and has challenged vaccine development (2). Synagis, a monoclonal antibody (MAb) directed against the RSV fusion protein, has shown prophylactic utility, but its cost and intramuscular route of administration have limited its use to hospitalized, high-risk infants Ͻ2 years of age (2). The only therapeutic intervention for RSV infection currently available to patients is the use of ribavirin (3), but its use is also limited because of poor efficacy and teratogenicity and the requirement of an aerosol and/or intravenous (i.v.) mode of administration in hospital settings (4). New therapeutic interventions able to lower the viral load, decrease transmission, and prevent lower respiratory complications are needed.RSV infection is initiated by attachment of the viral G protein to the surface of airway epithelial (AE) cells (5,6). Following attachment, the viral F protein mediates fusion of the viral and cellular membranes, allowing the RSV ribonucleic protein (RNP) complex, comprised of the viral RNA genome encapsulated with nucleoprotein (N) and associated with the phosphoprotein (P) and RNA-dependent RNA polymerase (L), to enter the cytoplasm. The RNP complex performs viral transcription to produce capped and polyadenylated mRNAs and genome replication. Detailed understanding of RSV biology is made difficult by the intimate coupling of transcription and replication activities. Furthermore, the RSV polymerase is large and complex, containing multiple domains and enzymatic activities that allow it to function and be

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“…The 5= triphosphorylated panhandle structure is efficiently recognized by retinoic acid-inducible gene I (RIG-I) and other cytoplasmic pattern recognition receptors, which in turn results in strong activation of innate immune responses and synthesis of type I and type III interferon (IFN) (reviewed in reference 12). To counteract the innate immune response, most mononegaviruses code for proteins with IFN-antagonistic activity, such as the V proteins of paramyxoviruses (7). Borna disease virus (BDV), the prototypic member of the family Bornaviridae, uses a completely different strategy for evading the innate immune response.…”

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confidence: 99%

Tick-Borne Nyamanini Virus Replicates in the Nucleus and Exhibits Unusual Genome and Matrix Protein Properties

Herrel

Hoefs

Staeheli

et al. 2012

J Virol

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Tick-borne Nyamanini virus (NYMV) is the prototypic member of a recently discovered genus in the order Mononegavirales , designated Nyavirus . The NYMV genome codes for six distinct genes. Sequence similarity and structural properties suggest that genes 1, 5, and 6 encode the nucleoprotein (N), the glycoprotein (G), and the viral polymerase (L), respectively. The function of the other viral genes has been unknown to date. We found that the third NYMV gene codes for a protein which, when coexpressed with N and L, can reconstitute viral polymerase activity, suggesting that it represents a polymerase cofactor. The second viral gene codes for a small protein that inhibits viral polymerase activity and further strongly enhances the formation of virus-like particles when coexpressed with gene 4 and the viral glycoprotein G. This suggests that two distinct proteins serve a matrix protein function in NYMV as previously described for members of the family Filoviridae . We further found that NYMV replicates in the nucleus of infected cells like members of the family Bornaviridae . NYMV is a poor inducer of beta interferon, presumably because the viral genome is 5′ monophosphorylated and has a protruding 3′ terminus as observed for bornaviruses. Taken together, our results demonstrate that NYMV possesses biological properties previously regarded as typical for filoviruses and bornaviruses, respectively.

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Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model

Cited by 87 publications

References 319 publications

Plasticity in Structural and Functional Interactions between the Phosphoprotein and Nucleoprotein of Measles Virus

Plasticity in Structural and Functional Interactions between the Phosphoprotein and Nucleoprotein of Measles Virus

The Interferon Type I/III Response to Respiratory Syncytial Virus Infection in Airway Epithelial Cells Can Be Attenuated or Amplified by Antiviral Treatment

Tick-Borne Nyamanini Virus Replicates in the Nucleus and Exhibits Unusual Genome and Matrix Protein Properties

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