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High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency
Chantal Emade Nkwelle1,2, Smith B Babiaka3,4, Clovis S Metuge2,3
1Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon.
Extracts from the tropical tree *Croton oligandrus* show potent HIV latency-reversal activity. These compounds may offer new avenues for HIV cure strategies by working through novel mechanisms and synergizing with existing treatments.
Area of Science:
- Phytochemistry
- Virology
- Immunology
Background:
- *Croton oligandrus* is a tropical tree used in traditional medicine.
- Other *Croton* species have demonstrated HIV latency-reversal properties.
- This study investigated *C. oligandrus* for similar anti-HIV potential.
Purpose of the Study:
- To identify extracts and compounds from *C. oligandrus* with HIV-1 latency-reversing activity.
- To evaluate the efficacy of these agents in J-Lat T cell lines.
- To elucidate the mechanisms of action involved in latency reversal.
Main Methods:
- Stem bark extraction using dichloromethane.
- In vitro testing on J-Lat T cells.
- Flow cytometry to measure GFP expression as a marker for HIV latency reversal.
Main Results:
- Four extracts demonstrated HIV latency reversal, with the most active showing 69.7% reversal at 1 µg/mL.
- Activity exceeded that of prostratin and *Croton megalobotrys* extract.
- Mechanisms involved pathways beyond protein kinase C (PKC) activation and histone deacetylase (HDAC) inhibition.
Conclusions:
- *C. oligandrus* extracts and compounds effectively reverse HIV latency in vitro.
- Novel mechanisms of action, including synergy with romidepsin, were observed.
- These findings suggest potential for *C. oligandrus* in developing adjunct therapies for HIV cure.
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