Document Detail


Macrophage internal HIV-1 is protected from neutralizing antibodies.
MedLine Citation:
PMID:  22205742     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In macrophages HIV-1 accumulates in intracellular vesicles designated virus containing compartments (VCC). These might play an important role in the constitution of macrophages as viral reservoirs and allow HIV-1 to evade the immune system by sequestration in an internal niche, which is difficult to access from the exterior. However until now, evidence if internal virus accumulations are protected from the host's humoral immune response is still lacking. In order to be able to study the formation and antibody accessibility of VCCs, we generated HIV-1 with GFP tagged Gag replicating in primary macrophages. Live cell observations revealed faint initial cytosolic Gag expression and subsequent large intracellular Gag accumulations which stayed stable over days. Taking advantage of the opportunity to study the accessibility of intracellular VCCs via the cell surface, we demonstrate that macrophage internal HIV-1 containing compartments cannot be targeted by neutralizing antibodies. Furthermore, HIV-1 was efficiently transferred from antibody treated macrophages to T-cells. Three dimensional reconstruction of electron microscopic slices revealed that Gag accumulations correspond to viral particles within enclosed compartments and convoluted membranes. Thus, although some VCCs were connected to the PM, the complex membrane architecture of the HIV-1 containing compartment might shield viral particles from neutralizing antibodies. In sum, our study provides evidence that HIV-1 is sequestered into a macrophage internal membranous web, posing an obstacle for the elimination of this viral reservoir.
Authors:
Herwig Koppensteiner; Carina Banning; Carola Schneider; Heinrich Hohenberg; Michael Schindler
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-28
Journal Detail:
Title:  Journal of virology     Volume:  -     ISSN:  1098-5514     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
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