Wild-type rabies virus phosphoprotein is associated with viral sensitivity to type I interferon treatment

Niu, Xuefeng; Tang, Lijun; Tseggai, Tesfai; Guo, Yi; Fu, Zhen F.

doi:10.1007/s00705-013-1743-2

Cited by 22 publications

(25 citation statements)

References 43 publications

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“…Alongside this, stimulation of an innate immune response to infection also seems comparable in both natural and experimental infection suggesting that regardless of exposure route, innate cell markers are activated in a conserved manner [45]. This latter feature corroborates with molecular experimentation investigating mechanisms of immune avoidance by the lyssaviruses as a genus [46,47,48,49]. …”

Section: Transmission and Maintenancesupporting

confidence: 61%

Lyssaviruses and Bats: Emergence and Zoonotic Threat

Banyard

Evans

Luo

et al. 2014

Viruses

102

105

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The continued detection of zoonotic viral infections in bats has led to the microbial fauna of these mammals being studied at a greater level than ever before. Whilst numerous pathogens have been discovered in bat species, infection with lyssaviruses is of particular significance from a zoonotic perspective as, where human infection has been reported, it is invariably fatal. Here we review the detection of lyssaviruses within different bat species and overview what is understood regarding their maintenance and transmission following both experimental and natural infection. We discuss the relevance of these pathogens as zoonotic agents and the threat of newly discovered viruses to human populations.

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Section: Transmission and Maintenancesupporting

confidence: 61%

Lyssaviruses and Bats: Emergence and Zoonotic Threat

Banyard

Evans

Luo

et al. 2014

Viruses

102

105

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“…In general, RABV street strains are more pathogenic than fixed viruses when inoculated via peripheral sites, and it is considered that evasion of innate immunity at peripheral sites (such as skin and muscles) is responsible for their high invasion into neurons from peripheral sites (Dietzschold et al, 2008). Moreover, a recent study showed that a street RABV strain (DRV strain) is more sensitive to IFN treatment than a laboratory-adapted fixed strain (B2C strain) and it was suggested that while street RABV strains are more sensitive to IFN treatment than laboratory-adapted RABV, they can strongly suppress IFN induction in host cells (Niu et al, 2013). Thus, the ability of the P protein to inhibit IKKe-mediated signalling may contribute to the strong interference with IFN induction by street viruses.…”

Section: Rabies Virus P Targets To Ikkementioning

confidence: 99%

Contribution of the interaction between the rabies virus P protein and I-kappa B kinase ϵ to the inhibition of type I IFN induction signalling

Masatani

Ozawa

Yamada

et al. 2016

Journal of General Virology

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The P protein of rabies virus (RABV) is known to interfere with the phosphorylation of the host IFN regulatory factor 3 (IRF-3) and to consequently inhibit type I IFN induction. Previous studies, however, have only tested P proteins from laboratory-adapted fixed virus strains, and to the best of our knowledge there is no report about the effect of P proteins from street RABV strains or other lyssaviruses on the IRF-3-mediated type I IFN induction system. In this study, we evaluated the inhibitory effect of P proteins from several RABV strains, including fixed and street virus strains and other lyssaviruses (Lagos bat, Mokola and Duvenhage viruses), on IRF-3 signalling. All P proteins tested inhibited retinoic acid-inducible gene-1 (RIG-I)-and TANK binding kinase 1 (TBK1)-mediated IRF-3-dependent IFN-b promoter activities. On the other hand, the P proteins from the RABV street strains 1088 and HCM-9, but not from fixed strains Nishigahara (Ni) and CVS-11 and other lyssaviruses tested, significantly inhibited I-kappa B kinase e (IKKe)-inducible IRF-3-dependent IFN-b promoter activity. Importantly, we revealed that the P proteins from the 1088 and HCM-9 strains, but not from the remaining viruses, interacted with IKKe. By using expression plasmids encoding chimeric P proteins from the 1088 strain and Ni strain, we found that the C-terminal region of the P protein is important for the interaction with IKKe. These findings suggest that the P protein of RABV street strains may contribute to efficient evasion of host innate immunity.

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“…DRV-Mexico is a wt RABV isolated from a rabid dog in Mexico in the 1990s (34). Recombinant CVSB2c expressing G [B2c(DRV-G)] or P [B2c(DRV-P)] from DRV-Mexico was constructed as described previously (35,36). Virus stocks were prepared in 1-day-old suckling mice as described previously (37).…”

mentioning

confidence: 99%

The Inability of Wild-Type Rabies Virus To Activate Dendritic Cells Is Dependent on the Glycoprotein and Correlates with Its Low Level of theDe Novo-Synthesized Leader RNA

Yang

Huang

Gnanadurai

et al. 2015

J Virol

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Dendritic cells (DCs) are the most efficient antigen-presenting cells, playing a key role in the adaptive immune responses to viral infections. Our studies demonstrate that wild-type (wt) rabies virus (RABV) does not activate DCs. Adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate virus neutralizing antibodies (VNA), or protect recipients against challenge. However, adoptive transfer of DCs primed with laboratory-attenuated RABV resulted in DC activation, production of VNA, and protection against challenge. In vitro studies with recombinant RABV (laboratory-attenuated RABV expressing the glycoprotein or the phosphoprotein from wt RABV) demonstrate that DC activation is dependent on the glycoprotein and involves the IPS-1 pathway. Furthermore, binding to and entry into DCs by wt RABV is severely blocked, and the copy number of de novo-synthesized leader RNA was two logs lower in DCs infected with the wt than in DCs treated with laboratory-attenuated RABV. However, transient transfection of DCs with synthesized leader RNA from either wt or attenuated RABV is capable of activating DCs in a dose-dependent manner. Thus, the inability of wt RABV to activate DCs correlates with its low level of the de novo-synthesized leader RNA. IMPORTANCERabies remains a public health threat, with more than 55,000 fatalities each year around the world. Since DCs play a key role in the adaptive immune responses to viral infections, we investigated the ability of rabies virus (RABV) to activate DCs. It was found that the adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate VNA, or protect mice against lethal challenge. However, laboratory-attenuated RABV mediates the activation of DCs via the IPS-1 pathway and is glycoprotein dependent. We further show that wt RABV evades DC-mediated immune activation by inefficient binding/entry into DCs and as a result of a reduced level of de novo-synthesized leader RNA. These findings may have important implications in the development of efficient rabies vaccines. Despite the fact that rabies is one of the oldest human infectious diseases, it continues to present a public health threat by causing more than 55,000 human deaths every year around the globe (1). Its causative agent, rabies virus (RABV), belongs to the Rhabdoviridae family, and its genome encodes five structural proteins in the order of nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA-dependent RNA polymerase (RdRp; also termed large protein [L]) (2). Among these, RABV G is the only viral protein that is glycosylated and exposed on the surface of the virion (3). RABV G is responsible for binding to neurospecific receptors, such as the acetylcholine receptor and neural cell adhesion molecule (NCAM), for invasion into the nervous system (4, 5). Moreover, RABV G is the only protein capable of inducing virus-neutralizing antibodies (VNA) that are protective against rabies (6-8).It has been known for a long time that most of the human rabies patient...

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Wild-type rabies virus phosphoprotein is associated with viral sensitivity to type I interferon treatment

Cited by 22 publications

References 43 publications

Lyssaviruses and Bats: Emergence and Zoonotic Threat

Lyssaviruses and Bats: Emergence and Zoonotic Threat

Contribution of the interaction between the rabies virus P protein and I-kappa B kinase ϵ to the inhibition of type I IFN induction signalling

The Inability of Wild-Type Rabies Virus To Activate Dendritic Cells Is Dependent on the Glycoprotein and Correlates with Its Low Level of theDe Novo-Synthesized Leader RNA

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