Document Detail


A novel motif in HIV-1 Nef that regulates MIP-1beta chemokine release in macrophages.
MedLine Citation:
PMID:  20504918     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
All primate lentiviruses encode Nef, an accessory protein that is important for viral pathogenicity in vivo. Lentiviral Nef proteins regulate the release of chemokines (MIP-1 alpha/beta) from infected macrophages, thereby enhancing virus dissemination (S. Swingler, A. Mann, J. Jacque, B. Brichacek, V. G. Sasseville, K. Williams, A. A. Lackner, E. N. Janoff, R. Wang, D. Fisher, and M. Stevenson, Nat. Med. 5:997-1003, 1999). In the current study, we have identified a novel domain within Nef (K(92)EK) that is required for Nef-dependent MIP-1beta production by infected macrophages. Mutations in this domain abrogated MIP-1beta induction but did not affect other Nef-ascribed activities, such as CD4 or major histocompatibility complex (MHC) class Iota downregulation. This further underscores Nef as a modular protein with genetically separable activities that may contribute to its role in viral replication and pathogenicity.
Authors:
Lue Dai; Mario Stevenson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-26
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-08-06     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8327-31     Citation Subset:  IM    
Affiliation:
University of Massachusetts Medical School, Program in Molecular Medicine, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Chemokine CCL4 / secretion*
HIV-1 / immunology*,  pathogenicity*
Humans
Macrophages / immunology*,  virology*
Molecular Sequence Data
Mutation, Missense
Protein Structure, Tertiary
Virulence Factors / genetics,  physiology*
nef Gene Products, Human Immunodeficiency Virus / genetics,  physiology*
Grant Support
ID/Acronym/Agency:
P30-AI42845/AI/NIAID NIH HHS; R01-AI032890/AI/NIAID NIH HHS; R01-MH64411/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CCL4; 0/Virulence Factors; 0/nef Gene Products, Human Immunodeficiency Virus; 0/nef protein, Human immunodeficiency virus 1
Comments/Corrections

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