CIIDI Scientists and Students Publish Study in Journal of Virus Eradication

Several CIIDI members and students conducted a study resulting in the publication of “Inhibition of protein kinase R suppresses HIV replication and integration in CD4 T cells” in the Journal of Virus Eradication.

Treatment of HIV infection using antiretroviral therapy can be very successful, leading to undetectable viral levels in patients who are compliant with their therapy. However, the infection remains present in the cells, preventing HIV cure. The mechanisms sustaining HIV-infected cell survival remain incompletely understood; thus, investigating the mechanisms of CD4 T cell survival and its interplay with HIV replication is critical for devising strategies against HIV infection.

In this study, the authors investigated the interplay between protein kinase R (PKR) and eukaryotic initiation factor-2α (eIF2α) in regulating HIV replication during the early stage of infection. They demonstrated that eIF2α is phosphorylated/activated in CD4 T cells during early HIV infection, and that PKR inhibition leads to a significant reduction in eIF2α phosphorylation and HIV p24 expression. PKR inhibition suppresses HIV replication and p24 expression by blocking HIV reverse transcription and integration. Based on these findings, the authors propose a working model for PKR inhibition and HIV suppression, shown to the right.
While further research is needed, the study presents a novel finding showing that PKR inhibition suppresses HIV replication and expression. PKR inhibitors have been utilized in other disease models, including neurodegenerative disorders and cancers, suggesting that targeting host PKR represents a potential therapeutic strategy against HIV infection.

Jaeden Pyburn, a PhD student in the Department of Biomedical Sciences, Dr. Juan Zhao, an assistant professor in the Department of Internal Medicine, and Dr. Ling
Wang, an associate professor also in the Department of Internal Medicine, share first authorship for this publication. Dr. Zhao and Dr. Zhi Q. Yao, a professor in the Department of Internal Medicine are the corresponding authors.

CIIDI Students and Members are in BOLD: Jaeden Pyburn, Juan Zhao, Ling Wang, Madison Schank, Addison C. Hill, Puja Banik, Yi Zhang, Xiao Y. Wu. Janet W. Lightner, Holly K. Orfield, Tabitha O. Leshaodo, Mohamed El Gazzar, Shunbin Ning, Jonathan P. Moorman, Zhi Q. Yao
CIIDI Scientists and Students Publish Study in Journal of Virus Eradication

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PKR inhibition decreases HIV-1 reverse transcription and inte-gration in HIV-infected CD4 T cells. A-B) HIV-1 infected CD4 T cells were treated with 1 μM PKR-IN-C16 for 48 h. Cells were collected (n = 6 biologically independent samples) for RT-PCR for R/U5 and LTR-gag. C) Alu-gag PCR analysis of HIV integration in HIV-infected CD4 T cells with or without PKR-IN-C16 treatment. Data were normalized by β-globin. D) A schematic model illustrating how PKR inhibition by PKR-IN-C16 reduces p24 levels in primary CD4 T cells during early HIV infection.