Date:
Thu, 23 Feb 2017 9:00 am - 10:00 am
Location:

Description

‘Targeting the HIV/pDC/IFN-I Axis to Reverse Hyper-Inflammation, Recover Anti-HIV-1 T Cells and Reduce HIV-1 Reservoirs’

Speaker:
Lishan Su, PhD
Professor, Department of Microbiology and Immunology
Lineberger Comprehensive Cancer Center
School of Medicine
University of North Carolina at Chapel Hill

Plasmacytoid dendritic cells (pDC) are the major type I interferon (IFN-I) producing cells and play important roles in antiviral immune responses. However, sustained pDC activation and IFN-I induction has been correlated with disease progression in chronic virus infection. We have recently defined the HIV-pDC-IFN axis in HIV-1 immuno-pathogenesis, and studied the mechanisms of pDC/IFN-induced immune suppression, and its role in HIV reservoir persistence.

During persistent HIV-1 infection, we have shown that blocking the IFN-I receptor (IFNAR) with an mAb (bAb) reversed HIV diseases in the presence of elevated HIV-1 replication in humanized mice, essentially “phenocopying” pDC depletion. In HIV-infected mice with cART, IFNAR bAb or pDC depletion induces HIV blips, associated with reversion of immune hyper-activation, functional recovery of human immune cells and reduction of HIV+ reservoirs.

We conclude that low levels of IFN-I signaling contribute to the immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a novel strategy to enhance immune recovery and to reduce HIV-1 reservoirs during suppressive cART. Our findings thus not only functionally define the role of pDC/IFN-I in HIV-1 disease progression, the IFNAR blocking and pDC-depleting mAb will also be developed into novel therapeutics to i) enhance immune recovery in immune non-responder patients under cART and ii) achieve control of HIV rebound after cART interruption.

Thursday February 23, 2017
9:00 - 10:00 a.m.
Location: 1131 Bioinformatics Building

Refreshments will be served

Location information

Bioinformatics Building

Country:
United States
County:
Orange
City:
27599 Chapel Hill

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