NDLI: Flavivirus Replication Complex Assembly Revealed by DNAJC14 Functional Mapping

Content Provider	PubMed Central
Author	Yi, Zhigang Yuan, Zhenghong Rice, Charles M. Macdonald, Margaret R.
Copyright Year	2012
Abstract	DNAJC14 is an Hsp40 family member that broadly modulates flavivirus replication. The mechanism by which DNAJC14 stoichiometrically participates in flavivirus replication complex (RC) formation is unknown; both reduced and elevated levels result in replication inhibition. Using yellow fever virus (YFV), we demonstrate that DNAJC14 redistributes and clusters with YFV nonstructural proteins via a transmembrane domain and a newly identified membrane-binding domain (MBD), which both mediate targeting to detergent-resistant membranes. Furthermore, the RC and DNAJC14 reside as part of a protein interaction network that remains after 1% Triton solubilization. Mutagenesis studies demonstrate that entry into this protein interaction network requires the DNAJC14 C-terminal self-interaction domain. Fusion of the DNAJC14 MBD and self-interaction domain with another Hsp40 family protein is sufficient to confer YFV-inhibitory activity. Our findings support a novel model of DNAJC14 action that includes specific membrane targeting of both DNAJC14 and YFV replication proteins, the formation of protein interactions, and a microdomain-specific chaperone event leading to RC formation. This process alters the properties of the RC membrane and results in the formation of a protein scaffold that maintains the RC.
Related Links	http://dx.doi.org/10.1128/jvi.01022-12
Ending Page	11832
Page Count	18
Starting Page	11815
File Format	PDF
ISSN	0022538X
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	21
Volume Number	86
Language	English
Publisher	American Society for Microbiology
Publisher Date	2012-11-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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Identification and Characterization of the Host Protein DNAJC14 as a Broadly Active Flavivirus Replication Modulator

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Identification and Characterization of the Host Protein DNAJC14 as a Broadly Active Flavivirus Replication Modulator

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