Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population

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Abstract

We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2′,5′-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS ( p = 0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position −88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS ( p = 0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.

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Most cited references 22

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Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

Christian Drosten, Stephan Günther, Wolfgang Preiser … (2003)

The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society

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A novel coronavirus associated with severe acute respiratory syndrome.

Thomas G Ksiazek, Dean Erdman, Cynthia Goldsmith … (2003)

A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population. A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus. Copyright 2003 Massachusetts Medical Society

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Antiviral actions of interferons.

C Samuel (2001)

Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.

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Author and article information

Contributors

Naoto Keicho

Journal

Journal ID (nlm-ta): Biochem Biophys Res Commun

Journal ID (iso-abbrev): Biochem. Biophys. Res. Commun

Title: Biochemical and Biophysical Research Communications

Publisher: Elsevier

ISSN (Print): 0006-291X

ISSN (Electronic): 1090-2104

Publication date PMC-release: 25 February 2005

Publication date (Print): 22 April 2005

Publication date (Electronic): 25 February 2005

Volume: 329

Issue: 4

Pages: 1234-1239

Affiliations

[a ]Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Japan

[b ]Bach Mai Hospital, Viet Nam

[c ]National Institute of Hygiene and Epidemiology, Viet Nam

[d ]Institute for Clinical Research in Tropical Medicine, Viet Nam

[e ]Hanoi-French Hospital, Viet Nam

[f ]The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Japan

[g ]Department of Infectious Diseases, Research Institute, International Medical Center of Japan, Japan

[h ]Research Institute, International Medical Center of Japan, Japan

[i ]International Medical Center of Japan, Japan

Author notes

[* ]Corresponding author. Fax: +81 3 3207 1038 nkeicho-tky@ 123456umin.ac.jp

Article

Publisher ID: S0006-291X(05)00361-X

DOI: 10.1016/j.bbrc.2005.02.101

PMC ID: 7092916

PubMed ID: 15766558

SO-VID: 143e66da-8875-464d-b227-b440dc135ddc

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Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population

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Abstract

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Microbiology Society: Coronaviruses

Most cited references 22

Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

A novel coronavirus associated with severe acute respiratory syndrome.

Antiviral actions of interferons.

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