Title

New and old players in HIV replication

Code

MOSY04

Session Type

Symposia Session

Venue

Casa del Diezmo 1 y 2

Date Time

Monday 22 July, 11:00 - 12:30

Co-Chairs:

Jonathan Karn, Case Western Reserve University, United States
Marina Lusic, Universitätsklinikum Heidelberg, Germany

This session will focus on recent developments in HIV molecular virology, including HIV entry, reverse transcription, integration, transcription, translation and budding. It will describe cellular and viral factors that enhance or inhibit HIV replication, and participants will discuss how these mechanisms can be harnessed to target viral replication and/or latency.

11:00 MOSY0401	Introduction

11:05 MOSY0402	Use of high-dimensional single-cell analysis to characterize cells latently infected with HIV Nadia Roan, University of California San Francisco, United States

11:20 MOSY0403	Evolutionary dynamics of HIV-1 reservoir cells Mathias Lichterfeld, Brigham and Women’s Hospital, United States

11:35 MOSY0404	HUSH antagonism by lentiviral proteins Florence Margottin-Goguet, Institut Cochin, France	Slides

11:50 MOSY0405	Molecular mechanisms shaping HIV proviral fate Ivan D'Orso, University of Texas Southwestern Medical Center, United States

12:05 MOSY0406	Questions and answers

12:25 MOSY0407	Closing remarks

AUTHOR

Elizabeth Wonderlich

SUMMARY

This session was chaired by Drs. Jonathan Karn and Marina Lusic and featured presentations that characterized and identified the HIV-1 proviral landscape, the cells that contain the HIV-1 reservoir, and host factors that may restrict or enhance viral replication.

HIGHLIGHTS

Dr. Nadia Roan presented her work characterizing phenotypes of single cells that contain latent HIV infection. Utilizing CyTOF and PP-SLIDE, she described a novel approach to predict the identity of HIV infected cells prior to viral reactivation and cellular stimulation remodeling. Dr. Mathias Lichterfeld’s work described his approach to characterizing the HIV-1 proviral landscape. Through FLIP-Seq, MIP-Seq, and ATAC-Seq, he showed that adults and infants on ART exhibit opposing proviral landscapes with regards to HIV-1 integration sites and orientations. Dr. Florence Margottin-Goguet presented her work showing a novel host restriction factor complex, HUSH, that can silence HIV-1 provirus and is antagonized by HIV-2/SIV Vpx and some HIV-1 Vpr proteins. Finally, Dr. Ivan D'orso implicated the host factor KAP-1 in enhancing transcriptional initiation from HIV-1 provirus.

CRITICAL ASSESSMENT

Drs. Roan and Lichterfeld’s work reveal that the latent reservoir remains a major barrier to HIV cure, a biomarker for latently infected cells remains elusive, and wide ranges of reservoir differences are found depending upon the donor and cell type assessed. The latent reservoir was assessed in cells that survived acute HIV-1 infection, leading to a possible survivor bias polarizing the presented data. Drs. Margottin-Goguet and D’orso revealed host factors that could be targets for drug inhibition or enhancement, but thus far methods of inhibition or enhancement are unknown and effects on healthy cells remain to be determined.