Unlike bacteria, viruses need a host to multiply. Human immunodeficiency virus type 1 (HIV-1) causes serious health problems worldwide, and eliminating the latent virus which is hiding in the body is one of the biggest challenges in the field. Viral replication, a process where the virus produces copies of itself, is regulated by a plethora of host pathways and proteins. Our body has a built-in circadian system which oscillates rhythmically and controls various biological processes, causing 24h rhythms in gene expression at the cellular level.
In this study published in the Journal of General Virology, the researchers from NDM's Chinese Academy of Medical Sciences Oxford Institute along with Nuffield Department of Clinical Medicine, Department of Pharmacology, Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, researchers found that salt-inducible kinases regulate rhythmic HIV - 1 replication.
They discovered that blocking salt inducible kinases with drugs or silencing their gene expression in cells disturbed the cellular clock and reduced the virus's ability to multiply. Importantly, it also hindered the virus from replicating in cells in a model of latent infection. The authors have previously published that circadian rhythms regulate HIV-1 replication and it is known that a specific class of enzymes called salt-inducible kinases are important for the circadian network. However, the link between HIV, circadian rhythms, and salt inducible kinases remained unknown.
This study shows that Salt Inducible Kinases play a crucial role in regulating HIV-1 replication and reactivation from latent infection. Overall, this paper stimulates further research to understand this process which could lead to new approaches for targeting latent infection. Many salt-inducible kinase inhibitors are currently under development for clinical use against different diseases. This suggests their therapeutic potential, however, future studies evaluating their importance for viral infections in a clinical setting are essential.
HIV-1 has been a significant global challenge for four decades, yet a definitive cure remains elusive. This underscores the critical role of interdisciplinary research including the fields of virology, circadian biology, and pharmacology, as demonstrated by the approach taken in this study.
Helene Borrmann, DPhil student in Professor McKeating’s lab and lead author of the paper, said: ‘Fundamental research is essential to understand the complexity of diseases like HIV-1, and this is what inspires me. Daily rhythms are everywhere and HIV has a worldwide impact, combining these broad concepts with the molecular understanding of cellular processes regulating diseases is truly fascinating.’
Professor Jane McKeating, Professor of Molecular Virology at NDM said: ‘The impact of the circadian clock to regulate our susceptibility to viruses and disease severity is only just being realised. Future research in this area is likely to uncover many new therapies.’