Regulation of CHMP4/ESCRT-III function in human immunodeficiency virus type 1 budding by CC2D1A
Authors
Usami, YoshikoPopov, Sergei
Weiss, Eric R.
Vriesema-Magnuson, Christie
Calistri, Arianna
Gottlinger, Heinrich G.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyProgram in Molecular Medicine
Program in Gene Function and Expression
Document Type
Journal ArticlePublication Date
2012-04-01Keywords
HIV-1Endosomal Sorting Complexes Required for Transport
DNA-Binding Proteins
Repressor Proteins
Genetics and Genomics
Virology
Metadata
Show full item recordAbstract
The detachment of human immunodeficiency type 1 (HIV-1) virions depends on CHPM4 family members, which are late-acting components of the ESCRT pathway that mediate the cleavage of bud necks from the cytosolic side. We now show that in human cells, CHMP4 proteins are to a considerable extent bound to two high-molecular-weight proteins that we have identified as CC2D1A and CC2D1B. Both proteins bind to the core domain of CHMP4B, which has a strong propensity to polymerize and to inhibit HIV-1 budding. Further mapping showed that CC2D1A binds to an N-terminal hairpin within the CHMP4 core that has been implicated in polymerization. Consistent with a model in which CC2D1A and CC2D1B regulate CHMP4 polymerization, the overexpression of CC2D1A inhibited both the release of wild-type HIV-1 and the CHMP4-dependent rescue of an HIV-1 L domain mutant by exogenous ALIX. Furthermore, small interfering RNA against CC2D1A or CC2D1B increased HIV-1 budding under certain conditions. CC2D1A and CC2D1B possess four Drosophila melanogaster 14 (DM14) domains, and we demonstrate that these constitute novel CHMP4 binding modules. The DM14 domain that bound most avidly to CHMP4B was by itself sufficient to inhibit the function of ALIX in HIV-1 budding, indicating that the inhibition occurred through CHMP4 sequestration. However, N-terminal fragments of CC2D1A that did not interact with CHMP4B nevertheless retained a significant level of inhibitory activity. Thus, CC2D1A may also affect HIV-1 budding in a CHMP4-independent manner.Source
J Virol. 2012 Apr;86(7):3746-56. Epub 2012 Jan 18. Link to article on publisher's siteDOI
10.1128/JVI.06539-11Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43973PubMed ID
22258254Notes
Co-author Eric Weiss is a student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/JVI.06539-11