Document Detail


Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus.
MedLine Citation:
PMID:  12388705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Productive entry of human immunodeficiency virus type 1 (HIV-1) into a host cell is believed to proceed via fusion of the viral envelope with the host cell's plasma membrane. Interestingly, the majority of HIV-1 particles that bind to the cell surface are taken up by the host cell via endocytosis; however, this mode of internalization generally does not result in infection. Presumably, virus particles remain trapped in the endocytic pathway and are eventually degraded. Here, we demonstrate that treatment of cells with various pharmacological agents known to elevate the pH of endosomes and lysosomes allows HIV-1 to efficiently enter and infect the host cell. Pretreatment of cells with bafilomycin A1 results in up to a 50-fold increase in the infectivity of HIV-1(SF2). Similarly, pretreatment of target cells with amantadine, concanamycin A, concanamycin B, chloroquine, and ammonium chloride resulted in increases in HIV-1 infectivity ranging between 2- and 15-fold. Analysis of receptor and coreceptor expression, HIV-long terminal repeat (LTR) transactivation, and transduction with amphotropic-pseudotyped murine leukemia virus (MLV)-based vectors suggests that the increase in infectivity is not artifactual. The increased infectivity under these conditions appears to be due to the ability of HIV-1 and MLV particles to enter via the endocytic pathway when spared from degradation in the late endosomes and lysosomes. These results could have significant implications for the administration of current and future lysosmotropic agents to patients with HIV disease.
Authors:
Brenda L Fredericksen; Bangdong L Wei; Jian Yao; Tianci Luo; J Victor Garcia
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  76     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-21     Completed Date:  2002-12-03     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11440-6     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
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MeSH Terms
Descriptor/Qualifier:
Amantadine / pharmacology
Animals
Anti-Bacterial Agents / pharmacology
Cell Line
Chloroquine / pharmacology
Endocytosis / drug effects*
Endosomes / metabolism*,  virology
HIV Long Terminal Repeat
HIV-1 / drug effects,  genetics,  pathogenicity*
HeLa Cells
Humans
Hydrogen-Ion Concentration
Leukemia Virus, Murine / genetics
Lysosomes / metabolism*,  virology
Macrolides*
Mice
Transduction, Genetic
Grant Support
ID/Acronym/Agency:
AI-33331/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Macrolides; 54-05-7/Chloroquine; 768-94-5/Amantadine; 88899-55-2/bafilomycin A1
Comments/Corrections

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