Berlinger, L

Rusert, P

Trkola, A

English

PubMed

L Berlinger

P Rusert

A Trkola

Springer - Publisher Connector

BioMed Central
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Retrovirology
Open AccessPoster presentation
P04-40. Dissecting pre- and post-attachment activity of HIV-1 entry 
inhibitors and neutralizing antibodies
L Berlinger*, P Rusert and A Trkola
Address: Institute of Medical Virology, University of Zurich, Zurich, Switzerland
* Corresponding author    
Background
HIV-1 adsorption and entry into target cells is initiated by
the binding of the viral envelope glycoprotein gp120 to
cell surface molecules. While the central role of CD4 as
entry receptor is undoubted, it has been debated for long
whether the initial contact of the virus with the target cell
occurs through interaction with CD4 itself or alternate
attachment molecules, such as heparan sulfate or adhe-
sions factors, as suggested by several studies. Here we
revisit this topic and dissect the actions of neutralizing
antibodies and inhibitors on initial attachment to the tar-
get cell, receptor engagement and fusion.
Methods
Attachment of GFP-labelled HIV particles to target cell
was assessed by flow cytometry. Virus entry was also quan-
tified by flow cytometry using a FRET-based virion fusion
assay. Infectivity was assessed using standard infection
assays using primary cells (PBMC) and cell lines (TZM-
bl).
Results
We found that the attachment process can only be success-
fully blocked by inhibitors that interfere with the engage-
ment of CD4 such as CD4bs specific Abs, soluble CD4
and CD4-specific inhibitors. Noteworthy, the MPER-spe-
cific neutralizing antibodies 2F5, 4E10 had no impact on
attachment but displayed potent inhibitory activity post
CD4 engagement. A survey of patient plasma confirmed a
high prevalence of antibody activity blocking virus attach-
ment suggesting CD4bs-directed activity but also revealed
the presence of a noteworthy post-CD4 engagement activ-
ity in several cases.
Conclusion
Our data indicate that attachment to target cells is almost
exclusively driven by the interaction with CD4. While
binding to other cell surface entities most certainly occur,
these interactions are not the driving factors that influence
the consecutive steps of the entry process. In addition the
careful dissection of antibody activity at specific steps of
virus attachment and entry allows insight into the func-
tional activity of the antibody response elicited during
natural infection.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P68 doi:10.1186/1742-4690-6-S3-P68
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P68
© 2009 Berlinger et al; licensee BioMed Central Ltd. 


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P04-40. Dissecting pre- and post-attachment activity of HIV-1 entry inhibitors and neutralizing antibodies

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