Jain, Pooja

Khan, Zafar K

Manuel, Sharrón L

Rahman, Saifur

Tangy, Frederic

Wigdahl, Brian

English

PubMed

Jain Pooja

Tangy Frederic

Wigdahl Brian

Khan Zafar K

Manuel Sharrón L

Rahman Saifur

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Retrovirology

Depletion of dendritic cells enhances susceptibility to cell-free but not cell-associated HTLV-1 infection in CD11c-DTR transgenic mice

Saifur Rahman

Sharrón L Manuel

Zafar K Khan

Brian Wigdahl

Frederic Tangy

Pooja Jain

Springer - Publisher Connector

MEETING ABSTRACT Open Access
Depletion of dendritic cells enhances
susceptibility to cell-free but not cell-associated
HTLV-1 infection in CD11c-DTR transgenic mice
Saifur Rahman1, Sharrón L Manuel1, Zafar K Khan1, Brian Wigdahl2, Frederic Tangy3, Pooja Jain1*
From 15th International Conference on Human Retroviruses: HTLV and Related Viruses
Leuven and Gembloux, Belgium. 5-8 June 2011
Human T-cell leukemia virus type 1 (HTLV-1) is asso-
ciated with two immunologically distinct diseases:
HTLV-1-associated myelopathy/tropical spastic para-
paresis (HAM/TSP) and adult T-cell leukemia (ATL).
The genesis of these diseases is believed to be asso-
ciated with the route (mucosa versus blood), mode
(cell-free versus cell-associated) of primary infection
and eventual modulation of dendritic cell (DC) func-
tions. To explore the role of DCs during early HTLV-1
infection in vivo, we used a chimeric HTLV-1 with a
replaced envelope gene from Moloney murine leuke-
mia virus to allow HTLV-1 to fuse with murine cells,
which are generally not susceptible to infection with
human retroviruses. We also used a CD11c-DTR trans-
genic mouse model system that permits the conditional
transient depletion of murine CD11c+ DCs. We
infected these transgenic mice with HTLV-1 using
both cell-free and cell-associated infection routes in
the absence and presence of DCs. The ablation of DCs
led to an enhanced susceptibility to infection with cell-
free, but not cell-associated HTLV-1 in both the CD4
and non-CD4 fractions, as measured by the proviral
load. Infection with cell-free virus in the absence of
DCs was also found to have increased levels of Tax
mRNA. Moreover, the depletion of DCs was found to
significantly dampen the cellular immune response
(IFN-g+CD8+ T cells) against both cell-free and cell-
associated virus. These results uniquely differentiate
the involvement of DCs in early cell-free compared
with late cell-associated HTLV-1 infection and
highlight a significant aspect of viral immunopathogen-
esis related to the progression of ATL and HAM/TSP
after the initial infection.
Author details
1Department of Microbiology and Immunology, and the Drexel Institute for
Biotechnology and Virology Research, Drexel University College of Medicine,
Doylestown, PA, 18902, USA. 2Department of Microbiology and Immunology,
and the Institute for Molecular Medicine and Infectious Disease, Drexel
University College of Medicine, Philadelphia, PA, 19102, USA. 3Unité de
Génomique Virale et Vaccination, URA-3015, Centre National de la Recherche
Scientifique (CNRS), Institut Pasteur, Paris, France.
Published: 6 June 2011
doi:10.1186/1742-4690-8-S1-A25
Cite this article as: Rahman et al.: Depletion of dendritic cells enhances
susceptibility to cell-free but not cell-associated HTLV-1 infection in
CD11c-DTR transgenic mice. Retrovirology 2011 8(Suppl 1):A25.
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* Correspondence: pooja.jain@drexelmed.edu
1Department of Microbiology and Immunology, and the Drexel Institute for
Biotechnology and Virology Research, Drexel University College of Medicine,
Doylestown, PA, 18902, USA
Full list of author information is available at the end of the article
Rahman et al. Retrovirology 2011, 8(Suppl 1):A25
http://www.retrovirology.com/content/8/S1/A25
© 2011 Rahman et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


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Depletion of dendritic cells enhances susceptibility to cell-free but not cell-associated HTLV-1 infection in CD11c-DTR transgenic mice

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