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Updated: Oct 15, 2026

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Reverse transcribed ssDNA derepresses translation of a retron antiviral protein
Karen Zhang1, Matías Rojas-Montero2, Darshini Poola2
1Gladstone Institutes, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Abstract:
Retrons are bacterial immune systems that prevent phage propagation by initiating a toxic response within infected hosts. Previously characterized retrons produce abundant multicopy single-stranded DNA (msDNA) by reverse transcription, which acts as an antitoxin in the absence of phage. However, we describe here a non-canonical mechanism for type VI retrons, which do not produce detectable msDNA in the absence of phage yet still provide defense. Focusing on Retron-Vpa2 from V. parahaemolyticus, we show broad defense against phages and identify triggers of the system when expressed in E. coli. Within the retron operon, we find a highly enriched, structured transcript that we term a hybrid RNA (hyRNA). The hyRNA contains the reverse transcription template and a toxin coding sequence that is repressed by a riboregulator. In our model of triggering, phage infection induces accumulation of msDNA, which hybridizes to the riboregulator and enables RNase H cleavage, derepressing translation of the toxin.
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