Biological properties of chimeric West Nile viruses

Borisevich, Victoria; Seregin, Alexey; Nistler, Ryan; Mutabazi, David; Yamshchikov, Vladimir

doi:10.1016/j.virol.2006.02.013

Cited by 34 publications

(22 citation statements)

References 59 publications

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“…Stocks of WNV strain NY99-385 were produced via transfection of plasmid-launched infectious clone pCMVNY99, as described below (37). All procedures involving infectious WNV were carried out in the Glaxo biosafety level 3 lab at the University of Alberta.…”

Section: Methodsmentioning

confidence: 99%

The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism

Urbanowski

Hobman

2013

J Virol

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West Nile virus (WNV) is a mosquito-transmitted pathogen that can cause serious disease in humans. Our laboratories are focused on understanding how interactions between WNV proteins and host cells contribute to virus replication and pathogenesis. WNV replication is relatively slow, and on the basis of earlier studies, the virus appears to activate survival pathways that delay host cell death during virus replication. The WNV capsid is the first viral protein produced in infected cells; however, its role in virus assembly is not required until after replication of the genomic RNA. Accordingly, from a temporal perspective, it is perfectly suited to block host cell apoptosis during virus replication. In the present study, we provide evidence that the WNV capsid protein blocks apoptosis through a phosphatidylinositol (PI) 3-kinase-dependent pathway. Specifically, expression of this protein in the absence of other viral proteins increases the levels of phosphorylated Akt, a prosurvival kinase that blocks apoptosis through multiple mechanisms. Treatment of cells with the PI 3-kinase inhibitor LY294002 abrogates the protective effects of the WNV capsid protein.

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Section: Methodsmentioning

confidence: 99%

The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism

Urbanowski

Hobman

2013

J Virol

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“…A plasmid expressing the fulllength genome of an attenuated Kunjin strain of WNV was also protective in mice [29]. Chimeric WNV strains have also been developed as candidate vaccines [30,31]. A YFV-WNV chimeric vaccine induced neutralizing antibodies and T cell responses, was completely protective against lethal WNV challenge in monkeys [30], and generated robust immune responses in healthy human volunteers [32].…”

Section: Introductionmentioning

confidence: 99%

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

Shrestha

Chu

et al. 2008

Vaccine

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West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (CNS) infection in humans and animals. Although commercial vaccines are available for horses, none is currently approved for human use. In this study, we evaluated the efficacy and mechanism of immune protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV vaccine induced higher levels of specific and neutralizing antibodies compared to a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial and almost complete protection against a highly stringent lethal intracranial WNV challenge were observed in mice 60 days after single dose immunization with the DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with a single dose of DNA plasmid or inactivated vaccine, antigenspecific CD8 + T cells were induced and contributed to protective immunity as acquired or genetic deficiencies of CD8 + T cells lowered the survival rates. In contrast, in boosted animals, WNVspecific antibody titers were higher, survival rates after challenge were greater, and an absence of CD8 + T cells did not appreciably affect mortality. Overall, our experiments suggest that in mice, both inactivated WNV and DNA plasmid vaccines are protective after two doses, and the specific contribution of antibody and CD8 + T cells to vaccine immunity against WNV is modulated by the prime-boost strategy.

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“…Different approaches have thus been used to improve the stability of full-length flavivirus cDNA clones [3]. Introns have been inserted to interrupt genes encoding products that may be toxic in bacteria [8,36], and relatively permissive E.coli strains have been identified. Full-length flavivirus cDNA from NY99, B956 and Kunjin WNV strains have previously been cloned in plasmids amplified in the HB101 E.coli strain [3,8,26].…”

Section: Discussionmentioning

confidence: 99%

“…Infectious clones of lineage 2, African strain B956 [26], lineage 1, American NY99 [1,3,30,36,43,50], and Australian Kunjin strains [8,40] have been generated and used to decipher the role of viral proteins in virulence [43,51], neuroinvasiveness [1,36] and escape from host defences [23,52], as well as to evaluate the impact of point mutations [23,53,54]. These tools have substantially facilitated identification of molecular determinants of WNV virulence, albeit in a non-European context.…”

Section: Discussionmentioning

confidence: 99%

IS-98-ST1 West Nile virus derived from an infectious cDNA clone retains neuroinvasiveness and neurovirulence properties of the original virus

Bahuon

Desprès

Pardigon

et al. 2012

Journal of Equine Veterinary Science

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Infectious clones of West Nile virus (WNV) have previously been generated and used to decipher the role of viral proteins in WNV virulence. The majority of molecular clones obtained to date have been derived from North American, Australian, or African isolates. Here, we describe the construction of an infectious cDNA clone of a Mediterranean WNV strain, IS-98-ST1. We characterized the biological properties of the recovered recombinant virus in cell culture and in mice. The growth kinetics of recombinant and parental WNV were similar in Vero cells. Moreover, the phenotype of recombinant and parental WNV was indistinguishable as regards viremia, viral load in the brain, and mortality in susceptible and resistant mice. Finally, the pathobiology of the infectious clone was examined in embryonated chicken eggs. The capacity of different WNV strains to replicate in embryonated chicken eggs closely paralleled their ability to replicate in mice, suggesting that inoculation of embryonated chicken eggs could provide a practical in vivo model for the study of WNV pathogenesis. In conclusion, the IS-98-ST1 infectious clone will allow assessment of the impact of selected mutations and novel genomic changes appearing in emerging European strains pathogenicity and endemic or epidemic potential. This will be invaluable in the context of an increasing number of outbreaks and enhanced severity of infections in the Mediterranean basin and Eastern Europe.

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Biological properties of chimeric West Nile viruses

Cited by 34 publications

References 59 publications

The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism

The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

IS-98-ST1 West Nile virus derived from an infectious cDNA clone retains neuroinvasiveness and neurovirulence properties of the original virus

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