Measles Virus Interaction with Host Cells and Impact on Innate Immunity

Gerlier, Denis; Valentin, Hélène

doi:10.1007/978-3-540-70523-9_8

Cited by 27 publications

(27 citation statements)

References 150 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The P-protein-STAT1/2 interaction inhibits IFN-activated nuclear translocation of STAT1/2 via the activity of a nuclear export sequence (NES) in the N-terminal region of P-protein (residues 49 to 58), which mediates active nuclear export of the P-protein-STAT1/2 complex, dependent on the activity of the cellular nuclear export protein CRM1 (37). The IFN antagonist proteins of several other viruses, including henipaviruses, Mapuera virus, measles virus, Ebola virus, and hepatitis C virus, also cause mislocalization of STAT1/2 (9,13,28,40,41), but RABV appears to be unique in that it selectively and directly targets the IFN-activated form of STAT1 (3,27,45). The evolution of this highly specific mechanism may relate to the limited coding capacity of the RABV genome (36), such that P-protein, which has several vital roles in genome replication in addition to IFN antagonism, is used to target STAT1/2 only when required.…”

Section: T He Principal Host Response To Viral Infection In Humans Ismentioning

confidence: 99%

Conservation of a Unique Mechanism of Immune Evasion across the Lyssavirus Genus

Wiltzer

Larrous

Oksayan

et al. 2012

J Virol

133

View full text Add to dashboard Cite

The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses.

show abstract

Section: T He Principal Host Response To Viral Infection In Humans Ismentioning

confidence: 99%

Conservation of a Unique Mechanism of Immune Evasion across the Lyssavirus Genus

Wiltzer

Larrous

Oksayan

et al. 2012

J Virol

133

View full text Add to dashboard Cite

show abstract

“…For MeV, the envelope contains hemagglutinin (H) and a fusion glycoprotein (F) that mediates tissue targeting and MeV entry (3)(4)(5). This process is coordinated by the matrix (M) protein, which also mediates packaging of nucleocapsid into virions by interacting with both glycoprotein tails and nucleoprotein (6). Nucleocapsids are filamentous, consisting of genomic RNA encapsidated into a regular helical array of N monomers.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…MV infects primarily hematopoietic and epithelial cells and causes a severe transient immune suppression facilitating secondary infections that is due to interference with both innate and adaptive immune responses, including the type I IFN network (20,23,38,39,61).…”

mentioning

confidence: 99%

Measles Virus C Protein Interferes with Beta Interferon Transcription in the Nucleus

Sparrer

Pfaller

Conzelmann

2012

J Virol

View full text Add to dashboard Cite

Transcriptional induction of beta interferon (IFN-␤) through pattern recognition receptors is a key event in the host defense against invading viruses. Infection of cells by paramyxoviruses, like measles virus (MV) (genus Morbillivirus), is sensed predominantly by the ubiquitous cytoplasmic helicase RIG-I, recognizing viral 5=-triphosphate RNAs, and to some degree by MDA5. While MDA5 activation is effectively prevented by the MV V protein, the viral mechanisms for inhibition of MDA5-independent induction of IFN-␤ remained obscure. Here, we identify the 186-amino-acid MV C protein, which shuttles between the nucleus and the cytoplasm, as a major viral inhibitor of IFN-␤ transcription in human cells. Activation of the transcription factor IRF3 by upstream kinases and nuclear import of activated IRF3 were not affected in the presence of C protein, suggesting a nuclear target. Notably, C proteins of wild-type MV isolates, which are poor IFN-␤ inducers, were found to comprise a canonical nuclear localization signal (NLS), whereas the NLSs of all vaccine strains, irrespective of their origins, were mutated. Site-directed mutagenesis of the C proteins from an MV wild-type isolate and from the vaccine virus strain Schwarz confirmed a correlation of nuclear localization and inhibition of IFN-␤ transcription. A functional NLS and efficient nuclear accumulation are therefore critical for MV C to retain its potential to downregulate IFN-␤ induction. We suggest that a defect in efficient nuclear import of C protein contributes to attenuation of MV vaccine strains.A ntiviral host defense relies on rapid recognition of invading viruses by pattern recognition receptors (PRRs), like the ubiquitous cytoplasmic RIG-I-like receptors (RLR), which include RIG-I, MDA5, and LGP-2, and a number of Toll-like receptors (TLR) operating mainly in specialized immune cells. Virus sensing by these receptors leads to activation of the transcription factors interferon regulatory factor 3 (IRF3) and IRF7 and nuclear factor kappa B (NF-B), which orchestrate transcriptional activation of type I interferons (alpha interferon [IFN-␣], IFN-␤, IFN-, and IFN-) and of proinflammatory cytokines (30, 43). Secreted early IFN-␤ alerts noninfected cells via binding to the IFN-␣ receptor (IFNAR) and activation of JAK/STAT signaling (50), which results in the induction of numerous IFN-stimulated genes (ISG). The established antiviral state limits further spread of the virus. As illustrated in the past decade, most viruses utilize multiple mechanisms to limit both the induction of and the response to type I IFN in order to be able to establish an infection (19,55,67). In the subfamily Paramyxovirinae, these functions are taken over by the diverse products of the phosphoprotein (P) gene (for a comprehensive review, see reference 22).Measles virus (MV) is a member of the genus Morbillivirus within the subfamily Paramyxovirinae and, in spite of the availability of safe live attenuated vaccines, remains a major cause of childhood mortality in developing countries (6...

show abstract

Measles Virus Interaction with Host Cells and Impact on Innate Immunity

Cited by 27 publications

References 150 publications

Conservation of a Unique Mechanism of Immune Evasion across the Lyssavirus Genus

Conservation of a Unique Mechanism of Immune Evasion across the Lyssavirus Genus

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

Measles Virus C Protein Interferes with Beta Interferon Transcription in the Nucleus

Contact Info

Product

Resources

About