Vpu and Tsg101 Regulate Intracellular Targeting of the Human Immunodeficiency Virus Type 1 Core Protein Precursor Pr55gag
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Published in | Journal of Virology Vol. 80; no. 8; pp. 3765 - 3772 |
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01.04.2006
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AbstractList | Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55gag. Depending on the cell type, Pr55gag accumulates either at the plasma membrane or on late endosomes/multivesicular bodies. Intracellular localization of Pr55gag determines the site of virus assembly, but molecular mechanisms that define cell surface or endosomal targeting of Pr55gag are poorly characterized. We have analyzed targeting of newly synthesized Pr55gag in HeLa H1 cells by pulse-chase studies and subcellular fractionations. Our results indicated that Pr55gag was inserted into the plasma membrane and, when coexpressed with the viral accessory protein Vpu, Pr55gag remained at the plasma membrane and virions assembled at this site. In contrast, Pr55gag expressed in the absence of Vpu was initially inserted into the plasma membrane, but subsequently endocytosed, and virus assembly was partially shifted to internal membranes. This endocytosis of Pr55gag required the host protein Tsg101. These results identified a previously unknown role for Vpu and Tsg101 as regulators for the endocytic uptake of Pr55gag and suggested that the site of HIV-1 assembly is determined by factors that regulate the endocytosis of Pr55gag. Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55 gag . Depending on the cell type, Pr55 gag accumulates either at the plasma membrane or on late endosomes/multivesicular bodies. Intracellular localization of Pr55 gag determines the site of virus assembly, but molecular mechanisms that define cell surface or endosomal targeting of Pr55 gag are poorly characterized. We have analyzed targeting of newly synthesized Pr55 gag in HeLa H1 cells by pulse-chase studies and subcellular fractionations. Our results indicated that Pr55 gag was inserted into the plasma membrane and, when coexpressed with the viral accessory protein Vpu, Pr55 gag remained at the plasma membrane and virions assembled at this site. In contrast, Pr55 gag expressed in the absence of Vpu was initially inserted into the plasma membrane, but subsequently endocytosed, and virus assembly was partially shifted to internal membranes. This endocytosis of Pr55 gag required the host protein Tsg101. These results identified a previously unknown role for Vpu and Tsg101 as regulators for the endocytic uptake of Pr55 gag and suggested that the site of HIV-1 assembly is determined by factors that regulate the endocytosis of Pr55 gag . Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55gag. Depending on the cell type, Pr55 gag accumulates either at the plasma membrane or on late endosomes/multivesicular bodies. Intracellular localization of Pr55 gag determines the site of virus assembly, but molecular mechanisms that define cell surface or endosomal targeting of Pr55gag are poorly characterized. We have analyzed targeting of newly synthesized Pr55 gag in HeLa H1 cells by pulse-chase studies and subcellular fractionations. Our results indicated that Pr55gag was inserted into the plasma membrane and, when coexpressed with the viral accessory protein Vpu, Pr55gag remained at the plasma membrane and virions assembled at this site. In contrast, Pr55gag expressed in the absence of Vpu was initially inserted into the plasma membrane, but subsequently endocytosed, and virus assembly was partially shifted to internal membranes. This endocytosis of Pr55gag required the host protein Tsg101. These results identified a previously unknown role for Vpu and Tsg101 as regulators for the endocytic uptake of Pr55gag and suggested that the site of HIV-1 assembly is determined by factors that regulate the endocytosis of Pr55gag. Copyright © 2006, American Society for Microbiology. All Rights Reserved. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI |
Author | Jorma Hinkula Ian Prior Maarit Suomalainen Kirsi Harila Antti Salminen Mathilda Sjöberg |
AuthorAffiliation | Department of Virology, Haartman Institute, FIN-00014 University of Helsinki, Finland, 1 The Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, United Kingdom, 3 Department of Biosciences at Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden, 2 Department of Virology, Swedish Institute for Infectious Disease Control and MTC, Karolinska Institutet, 171 82 Stockholm and Department of Molecular Virology, Linkoping University, 581 83 Linkoping, Sweden 4 |
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Keywords | Immunopathology Targeting Microbiology HIV-1 virus Retroviridae AIDS Immune deficiency Lentivirus Protein Virology Infection Virus Regulation(control) Viral disease Human immunodeficiency virus Intracellular |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Corresponding author. Mailing address: Department of Virology, Haartman Institute, P.O. Box 21, FIN-00014 University of Helsinki, Finland. Phone: 358-9-19126688. Fax: 358-9-19126491. E-mail: maarit.suomalainen@helsinki.fi. |
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Mendeley... Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55gag. Depending on the cell type, Pr55gag accumulates either... Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55 gag . Depending on the cell type, Pr55 gag accumulates... Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral core protein Pr55gag. Depending on the cell type, Pr55 gag accumulates either... |
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SubjectTerms | Biological and medical sciences Cell Membrane - metabolism DNA-Binding Proteins - physiology Endocytosis Endosomal Sorting Complexes Required for Transport Fundamental and applied biological sciences. Psychology Gene Products, gag - metabolism HeLa Cells HIV-1 - physiology Human Immunodeficiency Virus Proteins Human viral diseases Humans Infectious diseases Medical sciences MEDICIN Medicin och hälsovetenskap MEDICINE Microbiology Miscellaneous Protein Precursors - metabolism Structure and Assembly Transcription Factors - physiology Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Regulatory and Accessory Proteins - physiology Virion - physiology Virology Virus Assembly |
Title | Vpu and Tsg101 Regulate Intracellular Targeting of the Human Immunodeficiency Virus Type 1 Core Protein Precursor Pr55gag |
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