MR findings in Murray Valley encephalitis.
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Murray Valley encephalitis (MVE) is caused by a flavivirus related to West Nile and St. Louis encephalitis viruses. We report a case of MVE resulting in quadriplegia and respiratory failure. MR imaging demonstrated thalamic hyperintensity on T2-weighted images, with similar involvement of the red nucleus, substantia nigra, and cervical cord. These findings preceded serologic diagnosis and are similar to those of Japanese encephalitis. In the appropriate setting, thalamic T2 hyperintensity is suggestive of flavivirus infection. (+info)
Epizootic activity of Murray Valley encephalitis and Kunjin viruses in an aboriginal community in the southeast Kimberley region of Western Australia: results of mosquito fauna and virus isolation studies.
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We undertook annual surveys of flavivirus activity in the community of Billiluna in the southeast Kimberley region of Western Australia between 1989 and 2001 [corrected]. Culex annulirostris was the dominant mosquito species, particularly in years of above average rains and flooding. Murray Valley encephalitis (MVE) virus was isolated in 8 of the 13 years of the study from seven mosquito species, but more than 90% of the isolates were from Cx. annulirostris. The results suggest that MVE virus is epizootic in the region, w ith activity only apparent in years with average or above average rainfall and increased numbers of Cx. annulirostris. High levels of MVE virus activity and associated human cases were detected only once (in 1993) during the survey period. Activity of MVE virus could only be partially correlated with wet season rainfall and flooding, suggesting that a number of other factors must also be considered to accurately predict MVE virus activity at such communities. (+info)
The mechanism for efficient nucleocapsid (NC) uptake into flavivirus particles which form by budding through the membranes of the endoplasmic reticulum (ER) was investigated by using Murray Valley encephalitis virus as a model. Budding of flavivirus membranes is driven by the viral transmembrane proteins prM and E independently of NC interaction. We show that control of signalase cleavage of the multimembrane-spanning flavivirus polyprotein by the catalytic function of the viral protease is critical for efficient virus morphogenesis. In wild-type virus, signalase cleavage of prM remains inefficient until cleavage of capsid at the cytosolic side of the signal sequence separating the two proteins has occurred. This obligatory sequence of cleavages was uncoupled in a mutant virus with the consequence of greatly reduced incorporation of NC into budding membranes and augmented release of NC-free virus-like particles. Efficient signalase cleavage of prM in the mutant virus resulted in partial inhibition of cleavage of capsid by the viral NS2B-3 protease. Our results support a model for flavivirus morphogenesis involving temporal and spatial coordination of NC assembly and envelopment by regulated cleavages of an ER membrane-spanning capsid-prM intermediate. (+info)
In situ reactions of monoclonal antibodies with a viable mutant of Murray Valley encephalitis virus reveal an absence of dimeric NS1 protein.
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Studies on the NS1 protein of flaviviruses have concluded that formation of a stable homodimer is required for virus replication. However, previous work has reported that substitution of a conserved proline by leucine at residue 250 in NS1 of Kunjin virus (KUNV) eliminated dimerization, but allowed virus replication to continue. To assess whether this substitution has similar effects on other flaviviruses, it was introduced into an infectious clone of Murray Valley encephalitis virus (MVEV). Consistent with studies of KUNV, the mutant virus (MVEV(NS1-250Leu)) produced high levels of monomeric NS1 and the NS1 homodimer could not be detected. In contrast, wild-type MVEV cultures contained predominantly dimeric NS1. Retarded virus growth in Vero cells and loss of neuroinvasiveness for weanling mice revealed further similarities between MVEV(NS1-250Leu) and the corresponding KUNV mutant. To confirm that the lack of detection of dimeric NS1 in mutant virus samples was not due to denaturation of unstable dimers during Western blotting, a mAb (2E3) specific for the MVEV NS1 homodimer was produced. When NS1 protein was fixed in situ in mammalian and arthropod cells infected with wild-type or mutant virus, 2E3 reacted strongly with the former, but not the latter. These results confirmed that Pro(250) in NS1 is important for dimerization and that substitution of this residue by leucine represents a conserved marker of attenuation for viruses of the Japanese encephalitis virus serocomplex. The inability to detect dimeric NS1 in supernatant or cell monolayers of cultures productively infected with mutant virus also suggests that dimerization of the protein may not be essential for virus replication. (+info)
Crystal structure of the Murray Valley encephalitis virus NS5 methyltransferase domain in complex with cap analogues.
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We have determined the high resolution crystal structure of the methyltransferase domain of the NS5 polypeptide from the Murray Valley encephalitis virus. This domain is unusual in having both the N7 and 2'-O methyltransferase activity required for Cap 1 synthesis. We have also determined structures for complexes of this domain with nucleotides and cap analogues providing information on cap binding, based on which we suggest a model of how the sequential methylation of the N7 and 2'-O groups of the cap may be coordinated. (+info)
Structure of the Murray Valley encephalitis virus RNA helicase at 1.9 Angstrom resolution.
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Murray Valley encephalitis virus (MVEV), a mosquito-borne flavivirus endemic to Australia, is closely related to Japanese encephalitis virus and West Nile virus. Nonstructural protein 3 (NS3) is a multifunctional enzyme with serine protease and DEXH/D-box helicase domains, whose activity is central to flavivirus replication and is therefore a possible target for anti-flaviviral compounds. Cloning, purification, and crystal structure determination to 1.9 Angstrom resolution of the NS3 helicase of MVEV and characterization of its enzymatic activity is reported. Comparison with the structures of helicases from related viruses supports a possible mechanism of ATP hydrolysis-driven strand separation. (+info)
A glycosylated peptide in the West Nile virus envelope protein is immunogenic during equine infection.
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Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective values against Murray Valley encephalitis virus.
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