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August 17-18, 2017 | Toronto, Canada
ANNUAL BIOTECHNOLOGY CONGRESS
alliedacademies
Ann Biol Sci, 2017
ISSN: 2348-1927
To eradicate HIV in individuals on ART (antiretroviral
therapy), it is imperative to eliminate both CD4+ T cells
and myeloid cell reservoirs. Most research to-date has
focused on eliminating the latent reservoir of CD4+ T cells.
However, information regarding the potential elimination
of HIV-infected macrophages is lacking. We have previously
demonstrated that resistance of monocyte-derived
macrophages (MDMs) to Vpr-induced effects was attributed
to inhibitors of apoptosis (c-IAP-2) expression. These results
suggest that strategies based on suppressing IAP-1/2 by
its specific inhibitor, smac mimetics (SM) may be useful in
killing HIV-infected macrophages. Our results show that SM
do not affect uninfected normal MDMs but selectively kill in
vitro HIV-infected macrophages, and macrophages derived
from the HIV-infected patients. We also show that by using
HIV-GFP strain, SM induced apoptosis of HIV- infected
macrophages. In addition, HIV-chronically infected U1 cells
were highly susceptible to SM-induced apoptosis in contrast
to its corresponding U937 cells. We have investigated the
molecular mechanism governing selective apoptosis of HIV-
infected macrophages by SM. Our results show that SM
induced macrophage cell death through apoptosis and not
through necroptosis. Furthermore, SM-induced apoptosis in
HIV-infected macrophages is not mediated through TNF-α.
In addition, in vitro HIV infection inhibits expression of RIP-1,
RIP-3 and TRAF-1 and bid. Inhibition of Rip-1 by its inhibitor,
necrostatin, induced cell death in normal macrophages
following treatment with SM suggesting a key role for Rip-1 in
SM-induced killing of HIV-infected macrophages. Overall, the
results suggest that inhibitions of IAPs could be a potential
strategy to selectively kill HIV-infected macrophages.
Speaker Biography
Ashok Kumar is a Professor in the Department of Pathology and Laboratory Medicine
and in the Department of Biochemistry, Microbiology and Immunology at the Universi-
ty of Ottawa, Ontario, Canada. He is also a Senior Scientist at the Children’s Hospital of
Eastern Ontario, Research Institute, Ottawa, ON, Canada. His main research interests
are in the field of HIV immunopathogenesis, induction and regulation of apoptosis in
HIV-infected human macrophages, regulation of T helper cytokines in health and dis-
ease and Toll-like receptor signaling in healthy and HIV-infected innate immune cells
such as human macrophages and macrophage subsets.
e:
Ashok Kumar
Children’s Hospital of Eastern Ontario, Canada
Inhibition of the inhibitors of apoptosis (IAP) genes and selective apoptosis of
HIV-infected human macrophages
Ashok Kumar, Ann Biol Sci, 2017, 5:3
DOI: 10.21767/2348-1927-C1-002