Tracking HIV Rebound following Latency Reversal Using Barcoded HIV
| العنوان: | Tracking HIV Rebound following Latency Reversal Using Barcoded HIV |
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| المؤلفون: | Ren Sun, Yushen Du, Xiaomeng Wu, Tian-hao Zhang, Akira J. Shimizu, Adam J. Schrier, Jocelyn T. Kim, Paul A. Wender, Melanie Dimapasoc, Mohamed S.A. Soliman, Jerome A. Zack, Matthew D. Marsden |
| المصدر: | Cell Reports Medicine |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Synthetic protein, reservoir, Viral protein, Anti-HIV Agents, antiretroviral therapy, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Virus Replication, General Biochemistry, Genetics and Molecular Biology, Virus, Mice, Report, medicine, Animals, Humans, Latency (engineering), Protein Kinase C, latency, Kinase, business.industry, HIV, Virology, Antiretroviral therapy, cure, Virus Latency, humanized mice, Humanized mouse, LRA, HIV-1, Virus Activation, business, ART |
| الوصف: | Summary HIV latency prevents cure of infection with antiretroviral therapy (ART) alone. One strategy for eliminating latently infected cells involves the induction of viral protein expression via latency-reversing agents (LRAs), allowing killing of host cells by viral cytopathic effects or immune effector mechanisms. Here, we combine a barcoded HIV approach and a humanized mouse model to study the effects of a designed, synthetic protein kinase C modulating LRA on HIV rebound. We show that administration of this compound during ART results in a delay in rebound once ART is stopped. Furthermore, the rebounding virus appears composed of a smaller number of unique barcoded viruses than occurs in control-treated animals, suggesting that some reservoir cells that would have contributed virus to the rebound process are eliminated by LRA administration. These data support the use of barcoded virus to study rebound and suggest that LRAs may be useful in HIV cure efforts. Graphical Abstract Highlights A genetically barcoded HIV swarm has been constructed and characterized This swarm forms a latent reservoir in antiretroviral (ART)-treated humanized mice Administering an HIV latency-reversing agent (LRA) during ART delays rebound LRA administration during ART also reduces barcode diversity of rebounding virus Marsden et al. construct a barcoded HIV swarm to study HIV latency formation and rebound in humanized mice. They find that the administration of a PKC modulating HIV latency-reversing agent delays rebound and reduces the genetic diversity of rebounding virus when antiretroviral therapy is stopped, suggesting the reduction of the reservoir. |
| تدمد: | 2666-3791 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9abf7ba49db2195eb9019d5b27e8f2d https://pubmed.ncbi.nlm.nih.gov/33377133 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a9abf7ba49db2195eb9019d5b27e8f2d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 26663791 |
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