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Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis
The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key componen...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551943/ https://www.ncbi.nlm.nih.gov/pubmed/32916894 http://dx.doi.org/10.3390/v12091005 |
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author | Elliott, Jennifer L. Kutluay, Sebla B. |
author_facet | Elliott, Jennifer L. Kutluay, Sebla B. |
author_sort | Elliott, Jennifer L. |
collection | PubMed |
description | The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis. |
format | Online Article Text |
id | pubmed-7551943 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75519432020-10-14 Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis Elliott, Jennifer L. Kutluay, Sebla B. Viruses Review The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis. MDPI 2020-09-09 /pmc/articles/PMC7551943/ /pubmed/32916894 http://dx.doi.org/10.3390/v12091005 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Elliott, Jennifer L. Kutluay, Sebla B. Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis |
title | Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis |
title_full | Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis |
title_fullStr | Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis |
title_full_unstemmed | Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis |
title_short | Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis |
title_sort | going beyond integration: the emerging role of hiv-1 integrase in virion morphogenesis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551943/ https://www.ncbi.nlm.nih.gov/pubmed/32916894 http://dx.doi.org/10.3390/v12091005 |
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