Adaptation of a retroviral family to its host

We only turn the light on in the rooms we use when we are awake. Similarly, the genes in our genome are only expressed when needed in a given cell in the body. Each gene also harbours regulatory regions in the genome. Those regulatory regions are akin to light switches in a room, waiting to be engaged. All cells express their cell type specific transcriptional regulatory proteins which bind to the genomic switch regions and modulate gene expression, similar to the finger that flicks a light- switch ON or OFF. Retroviruses, like the Human Immunodeficiency Virus (HIV), lack their own transcriptional regulators. Instead, retroviruses adapted their own, very short regulatory or switch sequence to abuse its hosts cellular transcriptional regulators. This allows retroviral expression specifically in those cells the viruses indeed infect. Today, we understand little how retroviral switch regions adapted during evolution. Retroviruses are prevalent in the genome of fruit flies. These fly retroviruses emerged when a noninfective transposable element, related to retroviruses, stole the sequence encoding an envelope protein from another virus. Like this, it acquired the means to infect another cell. Our previous data shows that this novel retrovirus effectively spread and diversified into at least 27 highly related, retroviral and retroviral-like species. In specific conditions, ten different fly retrovirus species (encoding an envelope) are expressed in at least eight distinct subsets of ovarian somatic support cells. From there, they infect the developing germline. In contrast, several other retroviruses during evolution have independently lost their envelope, and hence also their infectivity. These derived retrovirus-like elements have concurrently adapted their expression to the germline tissue in the fly ovary where they replicate intracellularly. Like HIV, fly retroviruses highjack their hosts transcriptional regulators for their own expression. The size of this retroviral family and their diversification of expression patterns - via adapting their short switch regions - provides a unique and profound model system to study the evolution and function of viral switch regions. With the evolutionary pedigree of the retroviruses as a context, we seek to identify the essential switch regions in the viral DNA, to uncover which transcriptional host regulatory proteins are essential for viral expression and whether viral DNA and host regulatory proteins indeed interact directly in living fly ovarian cells. Our work will highlight how a viral family tapped into its hosts transcriptional regulation. Deciphering the combinatorial logic of the viral switch regions will provide fundamental insights into retroviral evolution and may be instrumental to understand the much larger regulatory regions controlling the host gene expression.

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