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PMID: 19403684 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Human immunodeficiency virus type 1 Nef protein targets CD4 to the multivesicular body pathway.

Journal of virology ·Vol. 83 ·No. 13 ·2009-07-00 ·Pages 6578-90

daSilva LL, Sougrat R, Burgos PV, Janvier K, Mattera R, Bonifacino JS

Abstract

The Nef protein of human immunodeficiency virus type 1 downregulates the CD4 coreceptor from the surface of host cells by accelerating the rate of CD4 endocytosis through a clathrin/AP-2 pathway. Herein, we report that Nef has the additional function of targeting CD4 to the multivesicular body (MVB) pathway for eventual delivery to lysosomes. This targeting involves the endosomal sorting complex required for transport (ESCRT) machinery. Perturbation of this machinery does not prevent removal of CD4 from the cell surface but precludes its lysosomal degradation, indicating that accelerated endocytosis and targeting to the MVB pathway are separate functions of Nef. We also show that both CD4 and Nef are ubiquitinated on lysine residues, but this modification is dispensable for Nef-induced targeting of CD4 to the MVB pathway.

MeSH Terms
CD4 Antigens/metabolism Down-Regulation Endosomes/metabolism HIV-1/metabolism HeLa Cells Humans Lysosomes/metabolism RNA Interference Ubiquitination nef Gene Products, Human Immunodeficiency Virus/metabolism
Chemicals
CD4 Antigens nef Gene Products, Human Immunodeficiency Virus nef protein, Human immunodeficiency virus 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
daSilva Luis L P
Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Building 18T, Room 101, National Institutes of Health, Bethesda, MD 20892, USA.
Sougrat Rachid
Burgos Patricia V
Janvier Katy
Mattera Rafael
Bonifacino Juan S
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.00548-09
Published
2009-07-00
Epub
2009-00-29
Pages
6578-90
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2698520
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1128/JVI.00548-09 PMC Full Text View journal details
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