TY - JOUR
T1 - A role for molecular chaperone Hsc70 in reovirus outer capsid disassembly
AU - Ivanovic, Tijana
AU - Agosto, Melina A.
AU - Chandran, Kartik
AU - Nibert, Max L.
PY - 2007/4/20
Y1 - 2007/4/20
N2 - After crossing the cellular membrane barrier during cell entry, most animal viruses must undergo further disassembly before initiating viral gene expression. In many cases, these disassembly mechanisms remain poorly defined. For this report, we examined a final step in disassembly of the mammalian reovirus outer capsid: cytoplasmic release of the central, δfragment of membrane penetration protein μ1 to yield the transcriptionally active viral core particle. An in vitro assay with reticulocyte lysate recapitulated the release of intact δ molecules. Requirements for activity in this system were shown to include a protein factor, ATP, and Mg2+ and K + ions, consistent with involvement of a molecular chaperone such as Hsc70. Immunodepletion of Hsc70 and Hsp70 impaired δ release, which was then rescued by addition of purified Hsc70. Hsc70 was associated with released δ molecules not only in the lysate but also during cell entry. We conclude that Hsc70 plays a defined role in reovirus outer capsid disassembly, during or soon after membrane penetration, to prepare the entering particle for gene expression and replication.
AB - After crossing the cellular membrane barrier during cell entry, most animal viruses must undergo further disassembly before initiating viral gene expression. In many cases, these disassembly mechanisms remain poorly defined. For this report, we examined a final step in disassembly of the mammalian reovirus outer capsid: cytoplasmic release of the central, δfragment of membrane penetration protein μ1 to yield the transcriptionally active viral core particle. An in vitro assay with reticulocyte lysate recapitulated the release of intact δ molecules. Requirements for activity in this system were shown to include a protein factor, ATP, and Mg2+ and K + ions, consistent with involvement of a molecular chaperone such as Hsc70. Immunodepletion of Hsc70 and Hsp70 impaired δ release, which was then rescued by addition of purified Hsc70. Hsc70 was associated with released δ molecules not only in the lysate but also during cell entry. We conclude that Hsc70 plays a defined role in reovirus outer capsid disassembly, during or soon after membrane penetration, to prepare the entering particle for gene expression and replication.
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U2 - 10.1074/jbc.M610258200
DO - 10.1074/jbc.M610258200
M3 - Article
C2 - 17284448
AN - SCOPUS:34249654610
SN - 0021-9258
VL - 282
SP - 12210
EP - 12219
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 16
ER -