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Molecular Determinants for Subcellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame 3b Protein ▿

Identifieur interne : 001E98 ( Ncbi/Curation ); précédent : 001E97; suivant : 001E99

Molecular Determinants for Subcellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame 3b Protein ▿

Auteurs : Eric C. Freundt ; Li Yu ; Elizabeth Park ; Michael J. Lenardo ; Xiao-Ning Xu

Source :

Journal of Virology [ 0022-538X ] ; 2009.

RBID : PMC:2698541

Descripteurs français

English descriptors

KwdEn :
- Active Transport, Cell Nucleus, Amino Acid Sequence, Animals, Cell Nucleus (metabolism), Chlorocebus aethiops, Humans, Mitochondria (metabolism), Mitochondrial Membranes (metabolism), Molecular Sequence Data, Mutagenesis, Site-Directed, Open Reading Frames, SARS Virus (genetics), SARS Virus (metabolism), Vero Cells, Viral Structural Proteins (genetics), Viral Structural Proteins (metabolism).
MESH :
- chemical , genetics : Viral Structural Proteins.
- genetics : SARS Virus.
- metabolism : Cell Nucleus, Mitochondria, Mitochondrial Membranes, SARS Virus, Viral Structural Proteins.
- Active Transport, Cell Nucleus, Amino Acid Sequence, Animals, Chlorocebus aethiops, Humans, Molecular Sequence Data, Mutagenesis, Site-Directed, Open Reading Frames, Vero Cells.

Abstract

Viruses such as hepatitis C and the severe acute respiratory syndrome coronavirus (SARS-CoV) encode proteins that are distributed between mitochondria and the nucleus, but little is known about the factors that control partitioning between these sites. SARS-CoV encodes a unique accessory gene called open reading frame (ORF) 3b that, like other unique accessory genes in SARS-CoV, likely contributes to viral pathogenicity. The ORF 3b protein is 154 amino acids and is predicted to express from the second ORF in subgenomic RNA3. In this report, we have characterized the molecular components that regulate intracellular localization of the ORF 3b protein. We demonstrate unique shuttling behavior of ORF 3b, whereby the protein initially accumulates in the nucleus and subsequently translocates to mitochondria. Following nuclear localization, ORF 3b traffics to the outer membrane of mitochondria via a predicted amphipathic α-helix. Additionally, ORF 3b contains a consensus nuclear export sequence, and we demonstrate that nuclear export and thus mitochondrial translocation are dependent on a leptomycin B-sensitive nuclear export mechanism. We further show that ORF 3b inhibits induction of type I interferon induced by retinoic acid-induced gene 1 and the mitochondrial antiviral signaling protein. Our observations provide insights into the cellular localization of ORF 3b that may enhance our understanding of the mechanisms by which ORF 3b contributes to SARS-CoV pathogenesis. The findings reported here reveal that for multilocalized proteins, consideration of the spatiotemporal distribution may be crucial for understanding viral protein behavior and function.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698541

DOI: 10.1128/JVI.00367-09
PubMed: 19403678
PubMed Central: 2698541

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Le document en format XML

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<front><div type="abstract" xml:lang="en"><p>Viruses such as hepatitis C and the severe acute respiratory syndrome coronavirus (SARS-CoV) encode proteins that are distributed between mitochondria and the nucleus, but little is known about the factors that control partitioning between these sites. SARS-CoV encodes a unique accessory gene called open reading frame (ORF) 3b that, like other unique accessory genes in SARS-CoV, likely contributes to viral pathogenicity. The ORF 3b protein is 154 amino acids and is predicted to express from the second ORF in subgenomic RNA3. In this report, we have characterized the molecular components that regulate intracellular localization of the ORF 3b protein. We demonstrate unique shuttling behavior of ORF 3b, whereby the protein initially accumulates in the nucleus and subsequently translocates to mitochondria. Following nuclear localization, ORF 3b traffics to the outer membrane of mitochondria via a predicted amphipathic α-helix. Additionally, ORF 3b contains a consensus nuclear export sequence, and we demonstrate that nuclear export and thus mitochondrial translocation are dependent on a leptomycin B-sensitive nuclear export mechanism. We further show that ORF 3b inhibits induction of type I interferon induced by retinoic acid-induced gene 1 and the mitochondrial antiviral signaling protein. Our observations provide insights into the cellular localization of ORF 3b that may enhance our understanding of the mechanisms by which ORF 3b contributes to SARS-CoV pathogenesis. The findings reported here reveal that for multilocalized proteins, consideration of the spatiotemporal distribution may be crucial for understanding viral protein behavior and function.</p>
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Molecular Determinants for Subcellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame 3b Protein ▿

Molecular Determinants for Subcellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame 3b Protein ▿

Source :

Descripteurs français

English descriptors

Abstract

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