Transgenic mice expressing a human poliovirus receptor: A new model for poliomyelitis

Ren, Ruibao; Costantini, Frank; Gorgacz, Edward J.; Lee, James J.; Racaniello, Vincent R.

doi:10.1016/0092-8674(90)90168-e

Cited by 361 publications

(252 citation statements)

References 25 publications

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“…Excellent transgenic (tg) mouse models have been developed to aid the study of the pathogenesis of poliomyelitis and its genetic determinants (12,13). The fact that PV-infected CD155 tg mice develop poliomyelitis bearing the hallmarks of the primate disease (12)(13)(14) underscores the cardinal role of receptor preference in EV disease specificity.…”

mentioning

confidence: 99%

A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice

Dufresne

Gromeier

2004

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

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Coxsackievirus A21 (CAV21) is classified within the species Human enterovirus C (HEV-C) of the Enterovirus genus of picornaviruses. HEV-C share striking homology with the polioviruses (PV), their closest kin among the enteroviruses. Despite a high level of sequence identity, CAV21 and PV cause distinct clinical disease typically attributed to their differential use of host receptors. PV cause poliomyelitis, whereas CAV21 shares a receptor and a propensity to cause upper respiratory tract infections with the major group rhinoviruses. As a model for CAV21 infection, we have developed transgenic mice that express human intercellular adhesion molecule 1, the cell-surface receptor for CAV21. Surprisingly, CAV21 administered to these mice via the intramuscular route causes a paralytic condition consistent with poliomyelitis. The virus appears to invade the CNS by retrograde axonal transport, as has been demonstrated to occur in analogous PV infections. We detected human intercellular adhesion molecule 1 expression on both transgenic mouse and human spinal cord anterior horn motor neurons, indicating that members of HEV-C may share PV's potential to elicit poliomyelitis in humans.

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mentioning

confidence: 99%

A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice

Dufresne

Gromeier

2004

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

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“…Structural as well as functional analyses indicate that the expression of the hPVR gene is controlled by a TATA and CAAT box-deficient promoter. Our results suggest that cis-acting elements of the hPVR core promoter and trans-acting factors available in cell lines of primate and mouse origin generally support hPVR expression, a result in concurrence with the expression of the hPVR gene in transgenic mice (24,25). However, the fine tuning of promoter activity of the hPVR gene may differ slightly depending on the cell type investigated.…”

mentioning

confidence: 57%

“…A very similar footprint pattern was obtained when the experiment was carried out with nuclear extracts of mouse L cells (data not shown), a result suggesting that factors controlling hPVR promoter activity and transcriptional start site selection are similar in human and mouse cells. This was not unexpected, since mice transgenic for the hPVR gene are not only sensitive to poliovirus infection, but when inoculated intravenously or intracerebrally, they produce a disease syndrome nearly identical to human poliomyelitis (24,25,41,42).…”

Section: Discussionmentioning

confidence: 99%

The Promoters for Human and Monkey Poliovirus Receptors

Solecki

Schwarz

Wimmer

et al. 1997

Journal of Biological Chemistry

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The cellular receptors for poliovirus (PVR) are glycoproteins belonging to the immunoglobulin superfamily. Functional receptors for poliovirus are only expressed by primates; known rodent homologues lack the ability to bind virus due to amino acid differences. Human poliovirus infections are targeted to the gastrointestinal tract and, rarely, to motor neurons in the central nervous system. Available evidence suggests that poliovirus uses only one cellular receptor, implying that the tissue tropism of poliovirus is likely to be related to the expression of the human PVR (hPVR). However, low levels of expression of hPVR-specific mRNAs can be detected in many human tissues other than the apparent target cells. The nonpathogenic function of hPVR is unknown. For a study of the transcriptional control of hPVR expression, we have isolated and characterized the promoter of the hPVR gene. Deletion analysis defined an approximately 280 base pair minimal promoter fragment that: 1) lacks TATA-and CAAT-like elements, 2) is distinguished by a high GC content, and 3) promotes transcription at multiple start sites. The pattern of activity caused by transfection of serial 5 -and 3 -promoter deletions is almost identical in HEp2, HeLa, COS-1, and mouse L929 cells, indicating a similar transcriptional regulation of the hPVR promoter in these cell lines. However, on transfection of Raji cells, a Burkitt's lymphoma cell line harboring a transcriptionally inactive hPVR gene, all promoter reporter constructs tested exerted only residual activity. These results suggest that the cis-element(s) governing cell type-specific hPVR expression resides in the minimal promoter region. We also report the sequences of the promoters of two monkey homologues to hPVR (AGM␣1 and AGM␣2).

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“…However, another picornavirus, coxsackie B virus (CBV) serotype 3, is recognized by TLR3 in infected cells and induces IFN-g as an effector for suppressing CBV infection (18). In this study, we analyzed in vivo infection of a popular picornavirus, PV, using PVR transgenic (PVRtg) mice, which show a neurotropic phenotype during PV infection similar to humans (19,20). Using this mouse model, in combination with TICAM-1 2/2 or IPS-1 2/2 mice, we present evidence that the host TICAM-1 pathway, particularly in macrophages (Mf), serves as a source of type I IFN induction and protects host PVRtg mice from PV infection and paralytic death.…”

Section: W Hen Rna Viruses Infect Mammalian Cells Type I Ifnmentioning

confidence: 99%

The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection

Oshiumi

Okamoto

Fujii

et al. 2011

The Journal of Immunology

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Cytoplasmic and endosomal RNA sensors recognize RNA virus infection and signals to protect host cells by inducing type I IFN. The cytoplasmic RNA sensors, retinoic acid inducible gene I/melanoma differentiation-associated gene 5, actually play pivotal roles in sensing virus replication. IFN-β promoter stimulator-1 (IPS-1) is their common adaptor for IFN-inducing signaling. Toll/IL-1R homology domain-containing adaptor molecule 1 (TICAM-1), also known as TRIF, is the adaptor for TLR3 that recognizes viral dsRNA in the early endosome in dendritic cells and macrophages. Poliovirus (PV) belongs to the Picornaviridae, and melanoma differentiation-associated gene 5 reportedly detects replication of picornaviruses, leading to the induction of type I IFN. In this study, we present evidence that the TLR3/TICAM-1 pathway governs IFN induction and host protection against PV infection. Using human PVR transgenic (PVRtg) mice, as well as IPS-1−/− and TICAM-1−/− mice, we found that TICAM-1 is essential for antiviral responses that suppress PV infection. TICAM-1−/− mice in the PVRtg background became markedly susceptible to PV, and their survival rates were decreased compared with wild-type or IPS-1−/− mice. Similarly, serum and organ IFN levels were markedly reduced in TICAM-1−/−/PVRtg mice, particularly in the spleen and spinal cord. The sources of type I IFN were CD8α+/CD11c+ splenic dendritic cells and macrophages, where the TICAM-1 pathway was more crucial for PV-derived IFN induction than was the IPS-1 pathway in ex vivo and in vitro analyses. These data indicate that the TLR3/TICAM-1 pathway functions are dominant in host protection and innate immune responses against PV infection.

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Transgenic mice expressing a human poliovirus receptor: A new model for poliomyelitis

Cited by 361 publications

References 25 publications

A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice

A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice

The Promoters for Human and Monkey Poliovirus Receptors

The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection

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