Guenthard, HF

Herbert, K

Joos, B

Krarup, A

Rusert, P

Trkola, A

Uhr, T

Weber, J

English

PubMed

P Rusert

A Krarup

B Joos

T Uhr

J Weber

K Herbert

HF Guenthard

A Trkola

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P09-02. Selection pressure of neutralizing antibodies and viral escape continues in late stages of the disease

Trkola A

Guenthard HF

Herbert K

Weber J

Uhr T

Joos B

Krarup A

Rusert P

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Retrovirology
Open AccessPoster presentation
P09-02. Selection pressure of neutralizing antibodies and viral 
escape continues in late stages of the disease
P Rusert*1, A Krarup1, B Joos1, T Uhr1, J Weber1, K Herbert2, HF Guenthard2 
and A Trkola1
Address: 1Institute for Medical Virology, University of Zürich, Zürich, Switzerland and 2Division of Infectious Diseases, University Hospital Zürich, 
Zürich, Switzerland
* Corresponding author    
Background
The neutralizing antibody response against HIV is subject
to constant viral escape. Viral escape from the autologous
neutralization response has been documented during
acute and chronic infection. Whether the successive adap-
tation between virus and antibody continues at the same
rate at later disease stages, is yet not known.
Methods
Here we analyzed the neutralization response of a rapidly
progressing, treatment naive individual over 1200 days
from the first presentation in our clinic with documented
acute infection until the patient's death. At 10 time points
spread over the entire observation period virus full length
envelope genes were cloned and sequenced. Altogether 26
envelope clones where obtained, analyzed for coreceptor
tropism and susceptibility to autologous antibody neu-
tralization in a pseudotyped virus inhibition assay.
Results
Analysis of plasma neutralization revealed an ongoing
antibody driven HIV-1 envelope evolution during the
entire disease course including the late symptomatic
phase. We found evidence for a strong selection pressure
on the V1/V2 loop based on the synonymous/nonsynon-
ymous mutation ratios throughout the entire observation
period, while the mutation rate within the V3 loop only
increased at later stages. Plasma antibodies were at all
time points capable of neutralizing preceding but not cur-
rent viral quasispecies, indicating that despite rapid CD4
decline (<200 past day 900) the humoral immune
response was functional and capable of adapting to new
emerging strains. For a brief period around day 900 a X4
using variant emerged that was completely resistant to the
antibodies from earlier time points but controlled subse-
quently.
Conclusion
Our study provides strong evidence that coevolution of
the viral envelope and antibody response against HIV-1
continues during all disease stages, and that the humoral
immune response is surprisingly apt to react to newly
evolving quasispecies even when CD4 T cells have dra-
matically declined.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P115 doi:10.1186/1742-4690-6-S3-P115
<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/P115
© 2009 Rusert et al; licensee BioMed Central Ltd. 


https://retrovirology.biomedcentral.com/track/pdf/10.1186/1742-4690-6-S3-P115?site=retrovirology.biomedcentral.com

P09-02. Selection pressure of neutralizing antibodies and viral escape continues in late stages of the disease

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