Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence

Horie, Hitoshi; Koike, Sachiko; Kurata, Takeshi; Sato-Yoshida, Y; Ise, Iku; Ota, Yojiro; Abe, S.; Hioki, Kyoji; Kato, Hiroyuki; Taya, Choji

doi:10.1128/jvi.68.2.681-688.1994

Cited by 90 publications

(52 citation statements)

References 33 publications

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“…Lack of expression of the PVR by nonprimate species has precluded the use of a small animal model for studies of immunity to poliomyelitis. However, the recent development of transgenic mice bearing the human poliovirus receptor (13)(14)(15) has provided us with a convenient small animal model for studies of immunity against poliovirus in a permissive host. Transgenic mice expressing the PVR and homozygous " The Poliovirus serotype, capsid protein, and peptide specificity of the T cell clones have previously been described (11).…”

Section: Resultsmentioning

confidence: 99%

“…Transgenic mice which expressed the human poliovirus receptor and H-2 a MHC class II genes, termed BALB/c ~, were derived from ICR mice transgenic for the PVR. Normal BALB/c mice were crossed with ICR PVR Tgl mice (13,15) and F1 hybrids expressing the PVR gene backcrossed with BALB/c. The progeny of the second generation were screened, using the polymerase chain reaction and restriction fragment polymorphism analysis, for the presence of the H-2 a MHC class II and PVR genes.…”

Section: Methodsmentioning

confidence: 99%

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Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor.

Mahon

Katrak

Nomoto

et al. 1995

The Journal of Experimental Medicine

108

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Sua'mmary The current understanding of the function of CD4 + T helper (Th) cells in immunity to infectious diseases is that Thl cells, which secrete interleukin (IL)-2 and interferon-3,, induce cellular immune responses, whereas Th2 cells, which secrete IL-4, IL-5, IL-6, and IL-10, provide helper function for humoral immunity. We have used a panel of poliovirus-specific murine CD4 + T cell clones and mice transgenic for the human poliovirus receptor to evaluate the role of Th cell subpopulations in protective immunity to poliovirus. The majority of T cell clones, as well as polyclonal T cells generated from mice infected or immunized with poliovirus, secreted IL-2 and interferon-q,, but not IL-4, IL-5, or IL-10, a profile typical of Thl cells. The Thl clones displayed major histocompatibility complex class II-restricted cytotoxic T lymphocyte activity against specific poliovirus peptide-pulsed target ceils, but also provided help for antipoliovirus neutralizing antibody production. To examine the mechanism of immunity in vivo, we have used poliovirus receptor-transgenic mice on a BALB/c (H-2 a) background. These animals developed a poliomyelitis-like disease when challenged intravenously with a virulent wild-type strain of poliovirus, but not with an attenuated vaccine strain. Furthermore, mice immunized with the vaccine strain were protected against a subsequent challenge with wild-type virus. Using an adoptive transfer technique, we demonstrated that it was possible to confer protection with primed B cells in the presence of polyclonal poliovirus-specific T cells, but not when transgenic mice received either B cells or T cells alone. Furthermore, protection was observed when mice received primed B cells in the presence of a VP4-specific Thl clone. The findings demonstrate that Thl cells can mediate a protective immune response against poliovirus infection in vivo through helper activity for humoral immunity and that CD4 § T cells, specific for the internal poliovirus capsid protein, VP4, can provide effective help for a protective antibody response directed against surface capsid proteins.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor.

Mahon

Katrak

Nomoto

et al. 1995

The Journal of Experimental Medicine

108

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“…Numerous studies show potential attenuating mutations for each serotype of OPV virus based on: (1) sequence comparisons between OPV virus strains and parental WPVs, (75,76) (2) sequence comparisons and/or neurovirulence testing in monkeys or mice of recombinant virus strains (i.e., swapping genetic segments between attenuated and neurovirulent strains) and/or site-directed mutants, (47,50,(77)(78)(79)(80)(81)(82)(83)(84) (3) OPV-related virus mutant strains after exposure to high temperature, (85) (4) OPV-related virus strains excreted by immunocompetent vaccine recipients without VAPP, (48,(86)(87)(88)(89) (5) OPV-related virus strains isolated from VAPP cases, (44)(45)(46)48,(90)(91)(92)(93)(94)(95)(96)(97)(98)(99) (6) strains isolated during cVDPV outbreaks, (15,57,100,101) (7) strains excreted by immunodeficient VDPV excretors, (102-106) (8) strains obtained during sequential passages after OPV administration in humans, (107) (9) strains obtained during sequential passages of OPV-related viruses in monkey tissues, (108) and (10) strains obtained from passages in cell culture. …”

Section: Attenuation and Reversionmentioning

confidence: 99%

Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

Tebbens¹,

Pallansch

Kim³

et al. 2013

Risk Analysis

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The live, attenuated oral poliovirus vaccine (OPV) provides a powerful tool for controlling and stopping the transmission of wild polioviruses (WPVs), although the risks of vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived poliovirus (cVDPV) outbreaks exist as long as OPV remains in use. Understanding the dynamics of cVDPV emergence and outbreaks as a function of population immunity and other risk factors may help to improve risk management and the development of strategies to respond to possible outbreaks. We performed a comprehensive review of the literature related to the process of OPV evolution and information available from actual experiences with cVDPV outbreaks. Only a relatively small fraction of poliovirus infections cause symptoms, which makes direct observation of the trajectory of OPV evolution within a population impractical and leads to significant uncertainty. Despite a large global surveillance system, the existing genetic sequence data largely provide information about transmitted virulent polioviruses that caused acute flaccid paralysis, and essentially no data track the changes that occur in OPV sequences as the viruses transmit largely asymptomatically through real populations with suboptimal immunity. We updated estimates of cVDPV risks based on actual experiences and identified the many limitations in the existing data on poliovirus transmission and immunity and OPV virus evolution that complicate modeling. Modelers should explore the space of potential model formulations and inputs consistent with the available evidence and future studies should seek to improve our understanding of the OPV virus evolution process to provide better information for policymakers working to manage cVDPV risks.

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“…Although they have served as a model organism to investigate anti-LAV immunity and evaluate LAV candidates in vivo [134,[146][147][148][149][153][154][155]183,184,193,194,[199][200][201], important limitations and concerns have stalled their use for this purpose. Despite sharing many physiologic and metabolic processes, mouse and man diverged evolutionarily more than 96 million years ago [202].…”

Section: Of Mice Men and Non-human Primatesmentioning

confidence: 99%

Humanized Mice for Live-Attenuated Vaccine Research: From Unmet Potential to New Promises

O'Connell

Douam

2020

Vaccines

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Live-attenuated vaccines (LAV) represent one of the most important medical innovations in human history. In the past three centuries, LAV have saved hundreds of millions of lives, and will continue to do so for many decades to come. Interestingly, the most successful LAVs, such as the smallpox vaccine, the measles vaccine, and the yellow fever vaccine, have been isolated and/or developed in a purely empirical manner without any understanding of the immunological mechanisms they trigger. Today, the mechanisms governing potent LAV immunogenicity and long-term induced protective immunity continue to be elusive, and therefore hamper the rational design of innovative vaccine strategies. A serious roadblock to understanding LAV-induced immunity has been the lack of suitable and cost-effective animal models that can accurately mimic human immune responses. In the last two decades, human-immune system mice (HIS mice), i.e., mice engrafted with components of the human immune system, have been instrumental in investigating the life-cycle and immune responses to multiple human-tropic pathogens. However, their use in LAV research has remained limited. Here, we discuss the strong potential of LAVs as tools to enhance our understanding of human immunity and review the past, current and future contributions of HIS mice to this endeavor.

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Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence

Cited by 90 publications

References 33 publications

Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor.

Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor.

Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

Humanized Mice for Live-Attenuated Vaccine Research: From Unmet Potential to New Promises

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