Elizabeth Wonderlich

This session was chaired by Drs. Florence Margottin-Goguet and Ivan D'orso and featured oral discussions of six poster presentations that focused on elucidating the mechanism of HIV latency at a transcriptional level. Characterization of factors regulating HIV transcription are crucial to optimize either permanent proviral silencing or efficient reactivation.

Using EDITS, Dr. Jonathan Karn presented estrogen-specific suppression of HIV reservoir measurements that may be related to decreased reservoir size or transcriptional induction. Mr. Jared Stern revealed a circadian cycle of cell-associated HIV RNA, with the peak occurring just before midnight. Dr. Maria Julia Ruiz revealed that central memory T cells initiate transcription, but experience a block in transcriptional elongation and completion that is overcome in effector memory T cells. By assessing ratios of unspliced and multispliced RNA and integegrated proviral DNA, Dr. Alexander Pasternak showed that transcriptional initiation is not stalled during HIV-1 latency. Dr. Deanna Kulpa presented that CD8+ T cells from HIV-uninfected donors suppress HIV-1 replication in antigen and cytolytic independent manners. Finally, Dr. Karn presented data showing that HIV infection induces viral latency by forcing memory T cells into a quiescent phenotype.

Dr. Karn’s work has yet to determine if estrogen effects clonal expansion, inducibility, or overall size of the reservoir. Although data from Drs. Ruiz and Pasternak agree that transcription initiation is not blocked, the exact point of HIV-1 replication that causes latency after initiation is not yet known. Although all data presented were incomplete narratives, these presentations revealed leading theories of transcriptional silencing related to HIV-1 latency. Combined, these data suggest there may be approaches to enhance latency to a permanently silenced state or reverse latency in strategies to eradicate HIV-1.