Tracking HIV Rebound following Latency Reversal Using Barcoded HIV

Matthew D Marsden; Tian-Hao Zhang; Yushen Du; Melanie Dimapasoc; Mohamed S A Soliman; Xiaomeng Wu; Jocelyn T Kim; Akira Shimizu; Adam Schrier; Paul A Wender; Ren Sun; Jerome A Zack

doi:10.1016/j.xcrm.2020.100162

Tracking HIV Rebound following Latency Reversal Using Barcoded HIV

Cell Rep Med. 2020 Dec 22;1(9):100162. doi: 10.1016/j.xcrm.2020.100162.

Authors

Matthew D Marsden¹, Tian-Hao Zhang², Yushen Du^{3

4}, Melanie Dimapasoc⁵, Mohamed S A Soliman⁵, Xiaomeng Wu⁵, Jocelyn T Kim⁶, Akira Shimizu⁷, Adam Schrier⁷, Paul A Wender⁷, Ren Sun³, Jerome A Zack^{5

8}

Affiliations

¹ Department of Microbiology and Molecular Genetics and Department of Medicine, Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
² Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Cancer Institute, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310058, China.
⁵ Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Departments of Chemistry and Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
⁸ Department of Medicine, Division of Hematology and Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

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.

Keywords: ART; HIV; LRA; antiretroviral therapy; cure; humanized mice; latency; protein kinase C; reservoir.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Anti-HIV Agents / pharmacology*
CD4-Positive T-Lymphocytes / drug effects
HIV Infections / drug therapy*
HIV-1 / drug effects*
Humans
Mice
Protein Kinase C / pharmacology
Virus Activation / drug effects
Virus Latency / drug effects*
Virus Replication / drug effects

Substances

Anti-HIV Agents
Protein Kinase C

Abstract

Publication types

MeSH terms

Substances

Grants and funding