Download 2015 department of medicine research day

2015 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Cocaine Modulation of Quiescent T Cells Enhances HIV Infection
Presenter: Dimitrios Vatakis
Division: Hematology-Oncology
☒Faculty ☐Fellow ☐Resident ☐Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☐Other
Principal Investigator/Mentor: Dimitrios Vatakis
Co-Investigators:
Thematic Poster Category: Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Atherosclerosis
Abstract
Stimulant use such as cocaine has been shown to impact the human immune system. In regards to
the human immunodeficiency virus (HIV) infection, a number of studies have indicated that cocaine
users are at an increased risk for infection and display more rapid disease progression and morbidity.
However due to many variables such as adherence to antiretroviral therapy, use of multiple classes of
drugs and co-infections among others, it is difficult to fully appreciate the impact drug abuse has on
HIV disease. We hypothesize that cocaine will influence the kinetics of HIV infection in quiescent cells
by increasing their permissiveness to infection. To this end, quiescent cells were exposed to cocaine
for three days. Based on our data, 3-day exposure, when compared to quiescent cells, resulted in
increased reverse transcription kinetics, higher levels of viral cDNA, increased viral RNA and protein
synthesis. In addition, the 3-day treated cells progressed to the G1b phase of the cell cycle and
displayed a marked increase in the levels of CCR5. The cocaine effects were mediated via the
Dopamine D4 and SIGMA-1 receptor pathways. The patterns of enhanced HIV infection were also
observed in vivo using BLT humanized mice. Acute cocaine exposure of mice resulted in increased
inflammation, accelerated kinetics of infection and higher viral loads. Thus, cocaine has a potentiating
effect of HIV replication through increased permissiveness of resting T cells and increased immune
activation.