PREreviews of “A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats” | PREreview

Skip to preprint details Skip to PREreviews

A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats

by Shelby Winans and Stephen P. Goff

Posted: January 12, 2021
Server: bioRxiv
DOI: 10.1101/2021.01.12.426369

Abstract

Retroviruses utilize the viral integrase (IN) protein to integrate a DNA copy of their genome into the host chromosomal DNA. HIV-1 integration sites are highly biased towards actively transcribed genes, likely mediated by binding of the IN protein to specific host factors, particularly LEDGF, located at these gene regions. We here report a dramatic redirection of integration site distribution induced by a single point mutation in HIV-1 IN. Viruses carrying the K258R IN mutation exhibit more than a 25-fold increase in integrations into centromeric alpha satellite repeat sequences, as assessed by both deep sequencing and qPCR assays. Immunoprecipitation studies identified host factors that uniquely bind to the mutant IN protein and thus may account for the novel bias for integration into centromeres. Centromeric integration events are known to be enriched in the latent reservoir of infected memory T cells, as well as in patients who control viral replication without intervention (so-called elite controllers). The K258R point mutation in HIV-1 IN reported in this study has also been found in databases of latent proviruses found in patients. The altered integration site preference induced by this mutation has uncovered a hidden feature of the establishment of viral latency and control of viral replication.

Read the preprint

1 Rapid PREreview

by Andrew Lopez

Where can I fill out a Rapid PREreview?

We’ve recently replaced Rapid PREreviews with Structured PREreviews.

You can write a Structured PREreview now.

We’ll be updating older Rapid PREreviews like these soon.

Aggregated Rapid PREreviews
Question	Yes	Unsure	N/A	No
Are the findings novel?	100%	0%	0%	0%
Are the results likely to lead to future research?	100%	0%	0%	0%
Is sufficient detail provided to allow reproduction of the study?	100%	0%	0%	0%
Are the methods and statistics appropriate for the analysis?	100%	0%	0%	0%
Are the principal conclusions supported by the data and analysis?	100%	0%	0%	0%
Does the manuscript discuss limitations?	100%	0%	0%	0%
Have the authors adequately discussed ethical concerns?	0%	0%	100%	0%
Does the manuscript include new data?	100%	0%	0%	0%
Are the data used in the manuscript available?	100%	0%	0%	0%
Is the code used in the manuscript available?	0%	0%	100%	0%
Would you recommend this manuscript to others?	100%	0%	0%	0%
Do you recommend this manuscript for peer review?	100%	0%	0%	0%

1 PREreview

Write a PREreview Request a PREreview

PREreview by Andrew Lopez

Authored by Andrew Lopez

Here, the authors seek to better understand the mechanism of Human Immunodeficiency Virus 1 (HIV-1) viral Integrase (IN). They hypothesize that four major sites on the C-terminal domain (CTD) are responsible for directing the viral integration site. They accomplish this by generating IN mutants at…

Read the PREreview by Andrew Lopez