Abstract
Foamy viruses (FV) are retroviruses belonging to the Spumaretrovirinae subfamily. They are non-pathogenic viruses endemic in several mammalian hosts like non-human primates, felines, bovines, and equines. Retroviral DNA integration is a mandatory step and constitutes a prime target for antiretroviral therapy. This activity, conserved among retroviruses and long terminal repeat (LTR) retrotransposons, involves a viral nucleoprotein complex called intasome. In the last decade, a plethora of structural insights on retroviral DNA integration arose from the study of FV. Here, we review the biochemistry and the structural features of the FV integration apparatus and will also discuss the mechanism of action of strand transfer inhibitors.
Highlights
The retroviridae family is a large group of viruses containing seven genera
X-ray the structure of the prototype foamy virus (PFV) intasome fundamentally changed the landscape in the field of retroviral integration, as it could both unravel the functional architecture of Determined by X-ray crystallography, the structure of the intasome fundamentally changed the integrationinapparatus and elucidate the mechanism of action
Co-crystallization of the PFV intasome with its target DNA allowed the visualization of both target capture complex (TCC) and strand transfer complex (STC) before and after the reaction, respectively [10,45]
Summary
The retroviridae family is a large group of viruses containing seven genera (alpha, beta, gamma, delta, epsilon lenti, and spuma-virus). One feature that distinguishes retroviruses from the other viruses is the ability to integrate their linear double stranded DNA into host cellular chromatin This essential activity is catalyzed by the virally encoded integrase (IN) protein and will lead to the covalent insertion of the provirus into the host genome [1]. The DNA cutting and strand transfer reactions occur through a similar mechanism between these genetics elements, the structure of DNA to be mobilized differs, i.e., IN cannot act on an already integrated DNA molecule and requires linear DNA to carry out the two essential sequential events, 30 processing, and strand transfer [3,4,5] These processes take place in the context of a nucleoprotein complex called intasome, consisting of the two viral DNA (vDNA). Was shown to be very amenable for structural biochemistry and was the source of many breakthroughs on the comprehension on the molecular basis of retroviral integration and strand transfer inhibitors resistance [8,9,10,11]
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