UNC HIV Cure Seminar Series

The next edition of the UNC HIV Cure Seminar Series will feature Ya-Chi Ho, MD, PhD, of Johns Hopkins University who will discuss “Cytotoxic T lymphocytes shape the landscape of HIV-1 proviruses.”

When Jan 26, 2017
from 09:00 AM to 10:00 AM
Where 1131 Bioinformatics
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Despite effective antiretroviral therapy, HIV-1 persists in memory CD4+ T cells creating a barrier to cure. The majority of HIV-1 proviruses are defective and are
generally considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective HIV-1 proviruses, we show that defective proviruses can be transcribed to RNAs that are spliced and translated. Proviruses can bypass major splice donors (MSDs) defects by activating novel splice sites to produce HIV-1 transcripts. Cells with HIV-1 proviruses containing defective MSDs can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs). Surprisingly, cells with proviruses containing lethal mutations upstream of CTL epitopes can also be recognized by CTLs potentially through aberrant translation. Thus, expression of defective proviruses complicates the measurement of the latent reservoir. CTLs may change the landscape of HIV-1 proviruses by preferential targeting cells with specific types of defective proviruses. The scope of potential CTL targets may be bigger than the size of the latent reservoir.

Refreshments will be served