Isolation of a measles virus variant: protection of newbornmice from measles encephalitis by 24 h prior intracerebralinoculation with the variant

Sakae, Hiroshi; Kohase, Masayoshi; Kurata, Takeshi; Yasuda, Hiroshi

doi:10.1007/s007050050212

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Infection of nontransgenic neonatal C57BL/6 animals with Ed MV has been reported to cause variable mortality rates ranging from 0 to 30% (41,42). Results of the present work are consistent with this low incidence of mortality, being 15 or 22% for NT mice infected with Ed MV or the N-522D variant, respectively.…”

Section: Discussionsupporting

confidence: 87%

hsp72, a Host Determinant of Measles Virus Neurovirulence

Carsillo

Traylor

Choi

et al. 2006

J Virol

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Transient hyperthermia such as that experienced during febrile episodes increases expression of the major inducible 70-kDa heat shock protein (hsp72). Despite the relevance of febrile episodes to viral pathogenesis and the multiple in vitro roles of heat shock proteins in viral replication and gene expression, the in vivo significance of virus-heat shock protein interactions is unknown. The present work determined the in vivo relationship between hsp72 levels and neurovirulence of an hsp72-responsive virus using the mouse model of measles virus (MV) encephalitis. Transgenic C57BL/6 mice were created to constitutively overexpress hsp72 in neurons, and these mice were inoculated intracranially with Edmonston MV (Ed MV) at 42 h of age. The mean viral RNA burden in brain was approximately 2 orders of magnitude higher in transgenic animals than in nontransgenic animals 2 to 4 weeks postinfection, and this increased burden was associated with a fivefold increase in mortality. Mice were also challenged with an Ed MV variant exhibiting an attenuated in vitro response to hsp72-dependent stimulation of viral transcription (Ed N-522D). This virus exhibited an attenuated neuropathogenicity in transgenic mice, where mortality and viral RNA burdens were not significantly different from nontransgenic mice infected with either Ed N-522D or parent Ed MV. Collectively, these results indicate that hsp72 levels can serve as a host determinant of viral neurovirulence in C57BL/6 mice, reflecting the direct influence of hsp72 on viral gene expression.Cellular heat shock proteins (HSPs) are recognized for their function as molecular chaperones that facilitate protein folding and trafficking (22) and for their ability to bind native proteins, resulting in altered activity of the substrate (18). Multiple families of HSPs are recognized and are classified according to their mass, with members of the 70-kDa family being expressed at high basal and/or stress-inducible levels in multiple tissues. In particular, the major inducible 70-kDa HSP (i.e., hsp72, also known as hsp70) exhibits a wide range of expression levels in the cytosol, being readily induced by physiological stimuli, such as fever (32,44). This dynamic range of expression and numerous roles in protein metabolism make hsp72 a potentially significant variable that could influence the outcome of viral replication in an animal host. In vitro studies suggest that hsp72 and the constitutively expressed isoform can directly modulate gene expression of several mammalian RNA and DNA viruses by supporting viral core protein maturation and/or assembly into nucleocapsid particles (11,12,30,31), by mediating assembly and/or activity of viral polymerase/replication complexes (7, 29, 45), or by mediating nuclear trafficking of viral preintegration complexes in the case of retroviruses (1). Despite the relevance of hsp72 to viral replication within the cell and the physiological relevance of elevated hsp72 to viral infection of an animal host, the biological (in vivo) significance of virus-hsp...

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Section: Discussionsupporting

confidence: 87%

hsp72, a Host Determinant of Measles Virus Neurovirulence

Carsillo

Traylor

Choi

et al. 2006

J Virol

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“…Neonatal C57BL/6 mice are susceptible to infection following intracranial inoculation with Edmonston MeV (Ed MeV), where neurons are the primary target of productive viral replication (9)(10)(11). Mice lack the constitutive expression of hsp70 that is observed in primates and other mammals (12)(13)(14).…”

mentioning

confidence: 99%

hsp70 and a Novel Axis of Type I Interferon-Dependent Antiviral Immunity in the Measles Virus-Infected Brain

Kim

Shu

Carsillo

et al. 2013

J Virol

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“…Mental retardation, seizure disorder, deafness and focal deficits are the common sequel 8 . Although, measles vaccination will prevent measles and hence measles encephalitis, animal studies are being undertaken to see if intracerebral inoculation of a variant virus or administration of monoclonal antibodies could prevent measles encephalitis 10,11 …”

Section: Discussionmentioning

confidence: 99%