Group Title: Infectious Agents and Cancer 2009, 4 (Suppl 2): P27
Title: Genetically restricted HIV-1 sub populations are associated with and migrate within metastatic sites of AIDS-related lymphoma
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 Material Information
Title: Genetically restricted HIV-1 sub populations are associated with and migrate within metastatic sites of AIDS-related lymphoma
Series Title: Infectious Agents and Cancer 2009, 4 (Suppl 2): P27
Physical Description: Archival
Creator: McGrath MS
Salemi M
Grey R
Galligan D
Lamers SL
Publication Date: 7/27/2009
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Bibliographic ID: UF00100216
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: Open Access: http://www.biomedcentral.com/info/about/openaccess/

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Poster presentation

Genetically restricted HIV-I sub populations are associated with
and migrate within metastatic sites of AIDS-related lymphoma
MS McGrath*2,3, M Salemi', R Grey', D Galligan2 and SL Lamers4


Address: 'Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA, 2Department of
Medicine, Heme-Onc Division, University of California, San Francisco, San Francisco, California, USA, 3The AIDS and Cancer Specimen Resource,
University of California, San Francisco, San Francisco, California, USA and 4BiolnfoExperts Inc., Gainesville, Florida, USA
* Corresponding author



from I Ith International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI): Basic, Epidemiologic, and Clinical
Research
Bethesda, MD, USA. 6-7 October 2008

Published: 17June 2009
Infectious Agents and Cancer 2009, 4(Suppl 2):P27 doi:10.1 186/1750-9378-4-S2-P27


This abstract is available from: http://www.infectagentscancer.com/content/4/S2/P27
2009 McGrath et al; licensee BioMed Central Ltd.


Background
AIDS-Related Lymphoma (ARL) is a disease mediated in
part by HIV-infected macrophages and persists despite
current HIV therapy protocols. The primary difference
between lymphoma seen in non HIV-infected individuals
and ARL is that ARL is uniformly high grade and widely
metastatic. This fact, coupled with finding almost 50 per-
cent of tumors have HIV expressing macrophages, has cre-
ated interest in studying a potential viral component to
lymphoma evolution. The expansion of HIV quasispecies
in vivo, which can be evaluated using a variety of compu-
tational algorithms, allows precise assignment of viral
evolutionary relationships when applied to sequences
obtained from multiple sites of infection. In this study, we
used an advanced HIV phylodynamic approach to track
the evolution of ARL metastasis in a multisite autopsy
study and identified a significant relationship between
HIV dynamics and lymphoma progression.

Methods
Multi-site frozen autopsy specimens were obtained
through the AIDS and Cancer Specimen Resource (ACSR)
from patients who died with ARL. A variety of lymphoid
and non-lymphoid tissues were classified as abnormal or
normal by histology examination and stained with anti-
bodies to CD68, MAC 387 and HIV p24. Quantitative HIV
genetic studies qualified diseased and non diseased tissues
to having > 1 copy of HIV/2000 genomic equivalents for
further genetic analyses. We extracted 406 HIV-1


genomes, spanning the 3' env-LTR segment of HIV that
were sequenced from multiple sites from two multi-site
autopsies. Viral dynamic analyses included phylogeny,
migration assessment, population growth and selection
studies using advanced bioinformatics methodologies.

Results
Detailed phylogenetic analysis clearly showed distinct
subpopulations of tumor and non-tumor viruses with
lymph node viruses moving between both groups. Gene
flow analysis showed that viruses from normal tissues
rarely migrated to lymphoma tissues (p < 0.0001). This
evidence strongly indicates a relationship between specific
HIV genetic variants and the development of tumors.
Additionally, a 10-fold faster evolution of viruses was
found within lymphoma tissues as compared to normal
tissues (median effective viral population in lymphoma
tissue = 60,000 compared to 6,000 in normal tissue) and
up to a four-fold increase in purifying selection in lym-
phoma viruses indicated that the lymphoma virus was
both fast replicating and genetically stable (non-tumor
dN/dS = 1.23 compared to tumor dN/dS = 0.26).

Conclusion
The results strongly support the existence of a fast replicat-
ing lymphoma-related virus, distinct from other circulat-
ing viruses in two patients who died with metastatic ARL.
The positive selection of viral sequences in one of the
cases suggests a non-random association of a lymphoma


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Infectious Agents and Cancer 2009, 4(Suppl 2): P27




specific viral element within viruses associated with tumor
metastasis. Earlier studies that localized HIV to tumor
associated macrophages suggests that this viral evolution
is relatively specific for a macrophage pool of viruses and
hence might be relatively resistant to current HAART ther-
apies dedicated at blocking primary infection rather than
eradicating macrophage associated infection. These data
suggest the addition of drugs that target infected macro-
phages may influence the evolution of ARL. Sequences
that cluster with ARL versus non tumor sites within these
two individuals are currently being evaluated to test
whether a true lymphoma virus might evolve in the con-
text of ARL lymphomagenesis.


http://www.infectagentscancer.com/content/4/S2/P27


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