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A Non-enveloped Virus Hijacks Host Disaggregation Machinery to Translocate across the Endoplasmic Reticulum Membrane.

Ravindran MS, Bagchi P, Inoue T, Tsai B - PLoS Pathog. (2015)

Bottom Line: Here we uncover a novel role of this machinery in driving membrane translocation during viral entry.Combining biochemical, cell-based, and imaging approaches, we find that the Hsp110 family member Hsp105 associates with the ER membrane J-protein B14.Hence the energy provided by the Hsc70-dependent Hsp105 disaggregation machinery can be harnessed to catalyze a membrane translocation event.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

ABSTRACT
Mammalian cytosolic Hsp110 family, in concert with the Hsc70:J-protein complex, functions as a disaggregation machinery to rectify protein misfolding problems. Here we uncover a novel role of this machinery in driving membrane translocation during viral entry. The non-enveloped virus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a critical infection step. Combining biochemical, cell-based, and imaging approaches, we find that the Hsp110 family member Hsp105 associates with the ER membrane J-protein B14. Here Hsp105 cooperates with Hsc70 and extracts the membrane-penetrating SV40 into the cytosol, potentially by disassembling the membrane-embedded virus. Hence the energy provided by the Hsc70-dependent Hsp105 disaggregation machinery can be harnessed to catalyze a membrane translocation event.

No MeSH data available.


Related in: MedlinePlus

A model depicting Hsp105-dependent extraction of SV40 from the ER into the cytosol.SV40 infection is initiated when the virus traffics from the cell surface to the ER (step 1). In the ER, specific ER-resident isomerase and reductase induce conformational changes to the virus, generating a hydrophobic particle (step 2). The hydrophobic virus then binds to and integrates into the ER membrane where SV40 accumulates into discrete foci (step 3). We envision that Hsp105, anchored to the membrane-bound J-protein B14 directly or indirectly via Hsc70/Hsp70, binds to the membrane-penetrating virus (step 4a, see insert). Continuous cycles of binding-release of SV40 by Hsp105-Hsc70 initiates the extraction process, a step that may be coupled to disassembly of the membrane-embedded viral particle (step 4b). Extraction is completed when SV40 is fully released into the cytosol (step 4c). Upon cytosol arrival, a partially disassembled viral particle intermediate mobilizes into the nucleus to stimulate infection (step 5).
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ppat.1005086.g006: A model depicting Hsp105-dependent extraction of SV40 from the ER into the cytosol.SV40 infection is initiated when the virus traffics from the cell surface to the ER (step 1). In the ER, specific ER-resident isomerase and reductase induce conformational changes to the virus, generating a hydrophobic particle (step 2). The hydrophobic virus then binds to and integrates into the ER membrane where SV40 accumulates into discrete foci (step 3). We envision that Hsp105, anchored to the membrane-bound J-protein B14 directly or indirectly via Hsc70/Hsp70, binds to the membrane-penetrating virus (step 4a, see insert). Continuous cycles of binding-release of SV40 by Hsp105-Hsc70 initiates the extraction process, a step that may be coupled to disassembly of the membrane-embedded viral particle (step 4b). Extraction is completed when SV40 is fully released into the cytosol (step 4c). Upon cytosol arrival, a partially disassembled viral particle intermediate mobilizes into the nucleus to stimulate infection (step 5).

Mentions: Our findings here establish an unanticipated role of an Hsp110 family member in driving membrane translocation of a viral particle. Specifically, we demonstrate that SV40 co-opts Hsp105 to cross the ER membrane and reach the cytosol in order to promote infection. SV40 infection begins when it traffics from the cell surface to the ER (Fig 6, step 1). In the ER, specific ER-resident isomerase and reductase act on the viral particle, imparting conformational changes to expose the hidden VP2/VP3 which generates a hydrophobic particle (Fig 6, step 2). The structurally altered virus then binds to and integrates into the ER membrane where SV40 accumulates into discrete foci (Fig 6, step 3). In our model, Hsp105, anchored to the membrane J-protein B14 directly or indirectly through Hsc70/Hsp70, binds to the membrane-penetrating virus (Fig 6, step 4a, see insert). Next, we hypothesize that iterative binding-release of SV40 by Hsp105-Hsc70 initiates the extraction process, a step that may involve disassembly of the membrane-embedded viral particle (step 4b). Extraction is completed when SV40 is fully released into the cytosol (step 4c). Upon cytosol arrival, a sub-viral particle intermediate is likely further processed to transport into the nucleus to cause infection (Fig 6, step 5).


A Non-enveloped Virus Hijacks Host Disaggregation Machinery to Translocate across the Endoplasmic Reticulum Membrane.

Ravindran MS, Bagchi P, Inoue T, Tsai B - PLoS Pathog. (2015)

A model depicting Hsp105-dependent extraction of SV40 from the ER into the cytosol.SV40 infection is initiated when the virus traffics from the cell surface to the ER (step 1). In the ER, specific ER-resident isomerase and reductase induce conformational changes to the virus, generating a hydrophobic particle (step 2). The hydrophobic virus then binds to and integrates into the ER membrane where SV40 accumulates into discrete foci (step 3). We envision that Hsp105, anchored to the membrane-bound J-protein B14 directly or indirectly via Hsc70/Hsp70, binds to the membrane-penetrating virus (step 4a, see insert). Continuous cycles of binding-release of SV40 by Hsp105-Hsc70 initiates the extraction process, a step that may be coupled to disassembly of the membrane-embedded viral particle (step 4b). Extraction is completed when SV40 is fully released into the cytosol (step 4c). Upon cytosol arrival, a partially disassembled viral particle intermediate mobilizes into the nucleus to stimulate infection (step 5).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4526233&req=5

ppat.1005086.g006: A model depicting Hsp105-dependent extraction of SV40 from the ER into the cytosol.SV40 infection is initiated when the virus traffics from the cell surface to the ER (step 1). In the ER, specific ER-resident isomerase and reductase induce conformational changes to the virus, generating a hydrophobic particle (step 2). The hydrophobic virus then binds to and integrates into the ER membrane where SV40 accumulates into discrete foci (step 3). We envision that Hsp105, anchored to the membrane-bound J-protein B14 directly or indirectly via Hsc70/Hsp70, binds to the membrane-penetrating virus (step 4a, see insert). Continuous cycles of binding-release of SV40 by Hsp105-Hsc70 initiates the extraction process, a step that may be coupled to disassembly of the membrane-embedded viral particle (step 4b). Extraction is completed when SV40 is fully released into the cytosol (step 4c). Upon cytosol arrival, a partially disassembled viral particle intermediate mobilizes into the nucleus to stimulate infection (step 5).
Mentions: Our findings here establish an unanticipated role of an Hsp110 family member in driving membrane translocation of a viral particle. Specifically, we demonstrate that SV40 co-opts Hsp105 to cross the ER membrane and reach the cytosol in order to promote infection. SV40 infection begins when it traffics from the cell surface to the ER (Fig 6, step 1). In the ER, specific ER-resident isomerase and reductase act on the viral particle, imparting conformational changes to expose the hidden VP2/VP3 which generates a hydrophobic particle (Fig 6, step 2). The structurally altered virus then binds to and integrates into the ER membrane where SV40 accumulates into discrete foci (Fig 6, step 3). In our model, Hsp105, anchored to the membrane J-protein B14 directly or indirectly through Hsc70/Hsp70, binds to the membrane-penetrating virus (Fig 6, step 4a, see insert). Next, we hypothesize that iterative binding-release of SV40 by Hsp105-Hsc70 initiates the extraction process, a step that may involve disassembly of the membrane-embedded viral particle (step 4b). Extraction is completed when SV40 is fully released into the cytosol (step 4c). Upon cytosol arrival, a sub-viral particle intermediate is likely further processed to transport into the nucleus to cause infection (Fig 6, step 5).

Bottom Line: Here we uncover a novel role of this machinery in driving membrane translocation during viral entry.Combining biochemical, cell-based, and imaging approaches, we find that the Hsp110 family member Hsp105 associates with the ER membrane J-protein B14.Hence the energy provided by the Hsc70-dependent Hsp105 disaggregation machinery can be harnessed to catalyze a membrane translocation event.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

ABSTRACT
Mammalian cytosolic Hsp110 family, in concert with the Hsc70:J-protein complex, functions as a disaggregation machinery to rectify protein misfolding problems. Here we uncover a novel role of this machinery in driving membrane translocation during viral entry. The non-enveloped virus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a critical infection step. Combining biochemical, cell-based, and imaging approaches, we find that the Hsp110 family member Hsp105 associates with the ER membrane J-protein B14. Here Hsp105 cooperates with Hsc70 and extracts the membrane-penetrating SV40 into the cytosol, potentially by disassembling the membrane-embedded virus. Hence the energy provided by the Hsc70-dependent Hsp105 disaggregation machinery can be harnessed to catalyze a membrane translocation event.

No MeSH data available.


Related in: MedlinePlus