A Perelson

A Williams

AJ McMichael

B Hahn

B Keele

BT Korber

C DeBoer

C Margaret

E Giorgi

G Ferrari

G Shaw

GH Learn

J Kopycinski

J Salazar

K Digleria

K Weinhold

M Cohen

MG Salazar

MK Liu

N Goonetilleke

P Borrow

P Hraber

RL Tanner

S Brackenridge

SL Campion

SR Moore

T Rostron

VE Bourne

VV Ganusov

Z Yu

Retrovirology

Springer - Publisher Connector

OA06-04. The role of early T-cell responses in subjects with acute HIV-1 infection

Liu, MK

Ferrari, G

Salazar, J

Keele, B

Tanner, RL

Hraber, P

Giorgi, E

Ganusov, VV

Learn, GH

Salazar, MG

Moore, SR

Digleria, K

Yu, Z

Rostron, T

DeBoer, C

Williams, A

Margaret, C

Kopycinski, J

Campion, SL

Bourne, VE

Brackenridge, S

Hahn, B

Cohen, M

Borrow, Persephone

Weinhold, K

Oxford University Research Archive

The role of early T-cell responses in subjects with acute HIV-1 infection

Borrow, P

Perelson, A

Shaw, G

Korber, BT

Goonetilleke, N

Mcmichael, AJ

Oxford University Research Archive (ORA)

Crossref

BioMed Central
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Retrovirology
Open AccessOral presentation
OA06-04. The role of early T-cell responses in subjects with acute 
HIV-1 infection
MK Liu*1, G Ferrari2, J Salazar3, B Keele3, RL Tanner1, P Hraber4, E Giorgi4, 
VV Ganusov4, GH Learn4, MG Salazar3, SR Moore1, K Digleria1, Z Yu1, 
T Rostron1, C DeBoer5, A Williams5, C Margaret5, J Kopycinski6, 
SL Campion1, VE Bourne1, S Brackenridge1, B Hahn3, M Cohen7, P Borrow1, 
K Weinhold2, A Perelson4, G Shaw3, BT Korber4, N Goonetilleke1 and 
AJ McMichael1
Address: 1Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, 2Duke University, Durham, NC, USA, 3University of 
Alabama, Birmingham, AL, USA, 4Los Alamos National Laboratory, Los Alamos, NM, USA, 5SCHARP, Seattle, WA, USA, 6Imperial College, 
London, UK and 7University of North Carolina, Chapel Hill, NC, USA
* Corresponding author    
Background
Previous studies have shown that T-cells play an impor-
tant role in the maintenance of virus set-point in early and
chronic HIV-1 infection. This study investigates the role of
the first T-cell responses in selecting virus escape and con-
trolling the early peak of viremia.
Methods
To identify the single transmitted/founder virus full-
length single genome amplification (SGA) virus sequenc-
ing was performed when patients were screened before
seroconversion during peak viremia. Virus evolution was
monitored by further serial SGA sequencing. Ex vivo IFN-γ
enzyme-linked immunospot assays and multi-parameter
flow cytometry were used with peptides matching the
founder virus sequence to comprehensively map the HIV-
1 specific T cell responses in subjects at serial time points
over the first 12 months post-screening.
Results
T-cell assays showed that HIV-1 specific T-cell responses
selected non-synonymous sequence changes at different
rates across the whole of the HIV-1 proteome. The first
detectable T-cell responses induced virus escape within
18–34 days of screening. However, these T-cell responses
were subsequently lost or diminished after the escape var-
iant became fixed within the virus population. The major-
ity of the later HIV-1 specific T-cell responses induced a
slower rate of escape, whilst a minority did not select for
escape variants over the study period. Selected sequence
changes could also be attributable to reversion, compen-
satory mutations, other immune responses and linkage to
other selected sites. Ongoing studies are exploring the
mechanisms behind the few rapid sequence changes
found where no T cell response could be identified.
Conclusion
The data shows that the first HIV-1 specific T-cell
responses can induce rapid virus escape at times earlier
than previously described. Appearing during the decline
of viral load from peak viremia these T-cell responses pro-
vide some evidence that they contribute to this fall. The
role of these first HIV-1 specific T-cell responses will have
an impact on vaccine design.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):O40 doi:10.1186/1742-4690-6-S3-O40
<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/O40
© 2009 Liu et al; licensee BioMed Central Ltd. 


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OA06-04. The role of early T-cell responses in subjects with acute HIV-1 infection

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