Author response: HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells
Year: 2015
Type: peer-review
Abstract: The human immunodeficiency virus (HIV) reproduces and spreads throughout the body by hijacking human immune cells and causing them to copy the virus’s genetic information. As the virus multiplies, it also causes the death of the immune system cells that help the human body recognize and eliminate viruses. This allows the virus to multiply unchecked. Studies of the genetic material of HIV – which is in the form of single-stranded RNA molecules and contains only a handful of genes – have begun to reveal how the virus can wreak such havoc to the human immune system. A small protein encoded by the virus, called Tat, boosts the expression of HIV genes in infected immune cells by binding to a structure that forms on newly synthesized viral RNAs. Recent evidence suggests that HIV also changes the expression of human genes to make immune cells more hospitable to the virus. However, it was not known exactly which specific genes are targeted, or how the virus alters their expression. Now, Reeder, Kwak et al. reveal how the Tat protein alters the expression of more than 400 human genes. Rather than bind to the same structure seen in newly forming HIV RNAs, Tat turns on or off the expression of its human target genes by interacting with proteins that regulate human gene expression. In doing so, Tat is able to precisely control the activity of an enzyme called RNA Polymerase II that is necessary for the early steps of gene expression. Tat’s multitasking ability – boosting HIV gene expression at the same time as reprogramming human gene expression – helps explain how a virus with so little genetic material of its own can perform such a wide range of activities in infected cells. The work of Reeder, Kwak et al. suggests that Tat reshapes the human genome to position target genes in ways that allow them to be efficiently turned on or off. Future studies will further reveal how Tat accomplishes this genome remodeling during different stages of infection. In addition, further research is also necessary to look closely into the sets of genes targeted by Tat to find patterns of genes that work together to alter cell behavior, and investigate how these new behaviors allow HIV to thrive.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2986651571