Studies on Neurovirulence in Poliovirus-Sensitive Transgenic Mice and Cynomolgus Monkeys for the Different Temperature-Sensitive Viruses Derived from the Sabin Type 3 Virus

Abe, S.; Ota, Yojiro; Doi, Yutaka; Nomoto, Akio; Nomura, Tatsuji; Chumakov, Konstantin; Hashizume, So

doi:10.1006/viro.1995.1327

Cited by 16 publications

(9 citation statements)

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“…21 The relative abundance of 472-C to 472-U in preparations of Sabin 3 correlates with neurovirulence in monkey and TgPVR21 mouse models. 23,24 The detection of 472-C revertant polioviruses in the stools of healthy vaccinees and cases of VAPP 25,20,26 indicates that neurological disease associated with OPV depends upon host factors, exactly as it does for wild poliovirus infection. 27 The strong circumstantial case for OPV causing transverse myelitis in a single patient has now been strengthened by the demonstration that the virus from this patient had the same neurovirulence in a transgenic mouse model as a virus of the same serotype known to have caused VAPP.…”

Section: Discussionmentioning

confidence: 99%

Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model

Thorley

Kelly

Nishimura

et al. 2009

Journal of Clinical Virology

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Section: Discussionmentioning

confidence: 99%

Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model

Thorley

Kelly

Nishimura

et al. 2009

Journal of Clinical Virology

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“…In the process of establishing the PVR-Tg mouse model, an appropriate Tg mouse strain (PVR-Tg21) that showed good sensitivity and clear dose-dependent response was chosen (49,50). In addition, many other investigations were performed, including correlation of neurovirulence levels of viruses in monkey and Tg mouse models (50,51) and selection of suitable inoculation routes (52).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…In addition, many other investigations were performed, including correlation of neurovirulence levels of viruses in monkey and Tg mouse models (50,51) and selection of suitable inoculation routes (52). Consequently, PVR-Tg mice became widely used to determine the neurovirulence levels of attenuated and neurovirulent strains of PV (50,51,(53)(54)(55). Analogous to another PVR-Tg mouse strain that expressed PVR at low levels and therefore did not show good sensitivity or dose-dependent response (49), it should be possible to improve the sensitivity of our hSCARB2-Tg mice by developing a new strain with higher hSCARB2 expression levels.…”

Section: Discussionmentioning

confidence: 99%

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Transgenic mouse model for the study of enterovirus 71 neuropathogenesis

Fujii¹,

Nagata

Sato

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

139

150

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Enterovirus 71 (EV71) typically causes mild hand-foot-and-mouth disease in children, but it can also cause severe neurological disease. Recently, epidemic outbreaks of EV71 with significant mortality have been reported in the Asia-Pacific region, and EV71 infection has become a serious public health concern worldwide. However, there is little information available concerning EV71 neuropathogenesis, and no vaccines or anti-EV71 drugs have been developed. Previous studies of this disease have used monkeys and neonatal mice that are susceptible to some EV71 strains as models. The monkey model is problematic for ethical and economical reasons, and mice that are more than a few weeks old lose their susceptibility to EV71. Thus, the development of an appropriate small animal model would greatly contribute to the study of this disease. Mice lack EV71 susceptibility due to the absence of a receptor for this virus. Previously, we identified the human scavenger receptor class B, member 2 (hSCARB2) as a cellular receptor for EV71. In the current study, we generated a transgenic (Tg) mouse expressing hSCARB2 with an expression profile similar to that in humans. Tg mice infected with EV71 exhibited ataxia, paralysis, and death. The most severely affected cells were neurons in the spinal cord, brainstem, cerebellum, hypothalamus, thalamus, and cerebrum. The pathological features in these Tg mice were generally similar to those of EV71 encephalomyelitis in humans and experimentally infected monkeys. These results suggest that this Tg mouse could represent a useful animal model for the study of EV71 infection.picornavirus | neurotropism | viral receptor E nterovirus 71 (EV71) is a human enterovirus species A of the genus Enterovirus within the Picornaviridae family, and it is known to be one of the causative agents of hand-foot-and-mouth disease (HFMD) (1, 2). HFMD is generally considered to be a mild exanthematous disease. However, in some infants and young children, after a few days of prodromal illness, HFMD caused predominantly by EV71 can be complicated by neurological manifestations, including ataxia, tremor, myoclonus, polio-like paralysis, encephalomyelitis, cardiopulmonary failure, and death (3, 4). In humans with fatal EV71 encephalomyelitis, inflammation and viral antigens in neurons were observed mainly in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus, and cerebrum (5, 6). Since the 1970s, HFMD outbreaks with significant mortality have been reported throughout the world, including in Bulgaria in 1975 [44 deaths (7) Appropriate animal models are needed to better understand EV71 neuropathogenesis and to facilitate the development of effective vaccines and drugs. EV71-infected cynomolgus monkeys developed neurological complications similar to those observed in human cases, including ataxia, tremor, and flaccid paralysis (11-15), and pathological lesions were observed in the spinal cord, brainstem, cerebellar dentate nucleus, and other parts of the brain (14,15). However, the use of monkeys to mod...

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“…Recently transgenic (Tg) mice that are susceptible to all three poliovirus serotypes have been generated by introducing the human gene for the poliovirus receptor (PVR) into the mouse genome (21,33). Cumulative evidence indicates that the Tg mice are a good second animal model for poliomyelitis (1,14). These observations demonstrate that PVR is one of the most important determinants of host specificity of the virus.…”

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confidence: 99%

Host range phenotype induced by mutations in the internal ribosomal entry site of poliovirus RNA

Shiroki

Ishii

Aoki

et al. 1997

J Virol

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Most poliovirus strains infect only primates. The host range (HR) of poliovirus is thought to be primarily determined by a cell surface molecule that functions as poliovirus receptor (PVR), since it has been shown that transgenic mice are made poliovirus sensitive by introducing the human PVR gene into the genome. The relative levels of neurovirulence of polioviruses tested in these transgenic mice were shown to correlate well with the levels tested in monkeys (H. Horie et al., J. Virol. 68:681-688, 1994). Mutants of the virulent Mahoney strain of poliovirus have been generated by disruption of nucleotides 128 to 134, at stem-loop II within the 5 noncoding region, and four of these mutants multiplicated well in human HeLa cells but poorly in mouse TgSVA cells that had been established from the kidney of the poliovirus-sensitive transgenic mouse. Neurovirulence tests using the two animal models revealed that these mutants were strongly attenuated only in tests with the mouse model and were therefore HR mutants. The virus infection cycle in TgSVA cells was restricted by an internal ribosomal entry site (IRES)-dependent initiation process of translation. Viral protein synthesis and the associated block of cellular protein synthesis were not observed in TgSVA cells infected with three of four HR mutants and was evident at only a low level in the remaining mutant. The mutant RNAs were functional in a cell-free protein synthesis system from HeLa cells but not in those from TgSVA and mouse neuroblastoma NS20Y cells. These results suggest that host factor(s) affecting IRES-dependent translation of poliovirus differ between human and mouse cells and that the mutant IRES constructs detect species differences in such host factor(s). The IRES could potentially be a host range determinant for poliovirus infection.

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Studies on Neurovirulence in Poliovirus-Sensitive Transgenic Mice and Cynomolgus Monkeys for the Different Temperature-Sensitive Viruses Derived from the Sabin Type 3 Virus

Cited by 16 publications

References 0 publications

Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model

Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model

Transgenic mouse model for the study of enterovirus 71 neuropathogenesis

Host range phenotype induced by mutations in the internal ribosomal entry site of poliovirus RNA

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