Protein expression from unintegrated HIV-1 DNA introduces bias in primary in vitro post-integration latency models

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F16%3A10330261" target="_blank" >RIV/00216208:11110/16:10330261 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1038/srep38329" target="_blank" >http://dx.doi.org/10.1038/srep38329</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/srep38329" target="_blank" >10.1038/srep38329</a>

Result language

angličtina

Original language name

Protein expression from unintegrated HIV-1 DNA introduces bias in primary in vitro post-integration latency models

Original language description

To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation. To discriminate between pre-and post-integration latency, integrase inhibitors are routinely used, preventing novel integrations upon cellular activation. Here, we show that this choice of antiretrovirals may still cause a bias of pre-integration latency in these models, as unintegrated HIV DNA can form and directly contribute to the levels of HIV RNA and protein production. We further show that the addition of reverse transcriptase inhibitors effectively suppresses the levels of episomal HIV DNA (as measured by 2-LTR circles) and decreases the levels of HIV transcription. Consequently, we show that latency levels described in models that only use integrase inhibitors may be overestimated. The inclusion of additional control conditions, such as 2-LTR quantification and the addition of reverse transcriptase inhibitors, is crucial to fully elucidate the actual levels of post-integration latency.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FN - Epidemiology, infection diseases and clinical immunology

OECD FORD branch

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Project

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Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2016

Confidentiality

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

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

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Volume of the periodical

6

Issue of the periodical within the volume

December

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

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UT code for WoS article

000389084200002

EID of the result in the Scopus database

2-s2.0-85002720227