Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F24%3A00600819" target="_blank" >RIV/67985904:_____/24:00600819 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/24:00600819

Výsledek na webu

<a href="https://www.mdpi.com/1999-4915/16/10/1518" target="_blank" >https://www.mdpi.com/1999-4915/16/10/1518</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/v16101518" target="_blank" >10.3390/v16101518</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting

Popis výsledku v původním jazyce

Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (gamma RVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity of gamma RVs can be attributed to this integration preference. In addition, long terminal repeats (LTRs) of some gamma RVs were shown to act as potent promoters by themselves. Here, we investigate the capacity of different gamma RV LTRs to drive stable expression within a non-preferred epigenomic environment in the context of diverse retroviral vectors. We demonstrate that different gamma RV LTRs are either rapidly silenced or remain active for long periods of time with a predominantly active proviral population under normal and retargeted integration. As an alternative to the established gamma RV systems, the feline leukemia virus and koala retrovirus LTRs are able to drive stable, albeit intensity-diverse, transgene expression. Overall, we show that despite the occurrence of rapid silencing events, most gamma RV LTRs can drive stable expression outside of their preferred chromatin landscape after retrovirus integrations.

Název v anglickém jazyce

Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting

Popis výsledku anglicky

Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (gamma RVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity of gamma RVs can be attributed to this integration preference. In addition, long terminal repeats (LTRs) of some gamma RVs were shown to act as potent promoters by themselves. Here, we investigate the capacity of different gamma RV LTRs to drive stable expression within a non-preferred epigenomic environment in the context of diverse retroviral vectors. We demonstrate that different gamma RV LTRs are either rapidly silenced or remain active for long periods of time with a predominantly active proviral population under normal and retargeted integration. As an alternative to the established gamma RV systems, the feline leukemia virus and koala retrovirus LTRs are able to drive stable, albeit intensity-diverse, transgene expression. Overall, we show that despite the occurrence of rapid silencing events, most gamma RV LTRs can drive stable expression outside of their preferred chromatin landscape after retrovirus integrations.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Viruses

ISSN

1999-4915

e-ISSN

1999-4915

Svazek periodika

16

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

17

Strana od-do

1518

Kód UT WoS článku

001342988200001

EID výsledku v databázi Scopus

2-s2.0-85207381776