Tetraspanins, Another Piece in the HIV-1 Replication Puzzle

Despite the great research effort placed during the last decades in HIV-1 study, still some aspects of its replication cycle remain unknown. All this powerful research has succeeded in developing different drugs for AIDS treatment, but none of them can completely remove the virus from infected patie...

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Main Authors: Henar Suárez, Vera Rocha-Perugini, Susana Álvarez, María Yáñez-Mó
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.01811/full
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author Henar Suárez
Vera Rocha-Perugini
Vera Rocha-Perugini
Susana Álvarez
María Yáñez-Mó
María Yáñez-Mó
author_facet Henar Suárez
Vera Rocha-Perugini
Vera Rocha-Perugini
Susana Álvarez
María Yáñez-Mó
María Yáñez-Mó
author_sort Henar Suárez
collection DOAJ
description Despite the great research effort placed during the last decades in HIV-1 study, still some aspects of its replication cycle remain unknown. All this powerful research has succeeded in developing different drugs for AIDS treatment, but none of them can completely remove the virus from infected patients, who require life-long medication. The classical approach was focused on the study of virus particles as the main target, but increasing evidence highlights the importance of host cell proteins in HIV-1 cycle. In this context, tetraspanins have emerged as critical players in different steps of the viral infection cycle. Through their association with other molecules, including membrane receptors, cytoskeletal proteins, and signaling molecules, tetraspanins organize specialized membrane microdomains called tetraspanin-enriched microdomains (TEMs). Within these microdomains, several tetraspanins have been described to regulate HIV-1 entry, assembly, and transfer between cells. Interestingly, the importance of tetraspanins CD81 and CD63 in the early steps of viral replication has been recently pointed out. Indeed, CD81 can control the turnover of the HIV-1 restriction factor SAMHD1. This deoxynucleoside triphosphate triphosphohydrolase counteracts HIV-1 reverse transcription (RT) in resting cells via its dual function as dNTPase, catalyzing deoxynucleotide triphosphates into deoxynucleosides and inorganic triphosphate, and as exonuclease able to degrade single-stranded RNAs. SAMHD1 has also been related with the detection of viral nucleic acids, regulating the innate immune response and would promote viral latency. New evidences demonstrating the ability of CD81 to control SAMHD1 expression, and as a consequence, HIV-1 RT activity, highlight the importance of TEMs for viral replication. Here, we will briefly review how tetraspanins modulate HIV-1 infection, focusing on the latest findings that link TEMs to viral replication.
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spelling doaj.art-1c2400ea76ab4d1192ba1379ba746df72022-12-22T03:31:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01811365560Tetraspanins, Another Piece in the HIV-1 Replication PuzzleHenar Suárez0Vera Rocha-Perugini1Vera Rocha-Perugini2Susana Álvarez3María Yáñez-Mó4María Yáñez-Mó5Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, SpainServicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, SpainVascular Pathophysiology Research Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, SpainServicio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, SpainDepartamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, SpainCentro de Biología Molecular Severo Ochoa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, SpainDespite the great research effort placed during the last decades in HIV-1 study, still some aspects of its replication cycle remain unknown. All this powerful research has succeeded in developing different drugs for AIDS treatment, but none of them can completely remove the virus from infected patients, who require life-long medication. The classical approach was focused on the study of virus particles as the main target, but increasing evidence highlights the importance of host cell proteins in HIV-1 cycle. In this context, tetraspanins have emerged as critical players in different steps of the viral infection cycle. Through their association with other molecules, including membrane receptors, cytoskeletal proteins, and signaling molecules, tetraspanins organize specialized membrane microdomains called tetraspanin-enriched microdomains (TEMs). Within these microdomains, several tetraspanins have been described to regulate HIV-1 entry, assembly, and transfer between cells. Interestingly, the importance of tetraspanins CD81 and CD63 in the early steps of viral replication has been recently pointed out. Indeed, CD81 can control the turnover of the HIV-1 restriction factor SAMHD1. This deoxynucleoside triphosphate triphosphohydrolase counteracts HIV-1 reverse transcription (RT) in resting cells via its dual function as dNTPase, catalyzing deoxynucleotide triphosphates into deoxynucleosides and inorganic triphosphate, and as exonuclease able to degrade single-stranded RNAs. SAMHD1 has also been related with the detection of viral nucleic acids, regulating the innate immune response and would promote viral latency. New evidences demonstrating the ability of CD81 to control SAMHD1 expression, and as a consequence, HIV-1 RT activity, highlight the importance of TEMs for viral replication. Here, we will briefly review how tetraspanins modulate HIV-1 infection, focusing on the latest findings that link TEMs to viral replication.https://www.frontiersin.org/article/10.3389/fimmu.2018.01811/fulltetraspaninsHIVentryassemblybuddingreverse transcription
spellingShingle Henar Suárez
Vera Rocha-Perugini
Vera Rocha-Perugini
Susana Álvarez
María Yáñez-Mó
María Yáñez-Mó
Tetraspanins, Another Piece in the HIV-1 Replication Puzzle
Frontiers in Immunology
tetraspanins
HIV
entry
assembly
budding
reverse transcription
title Tetraspanins, Another Piece in the HIV-1 Replication Puzzle
title_full Tetraspanins, Another Piece in the HIV-1 Replication Puzzle
title_fullStr Tetraspanins, Another Piece in the HIV-1 Replication Puzzle
title_full_unstemmed Tetraspanins, Another Piece in the HIV-1 Replication Puzzle
title_short Tetraspanins, Another Piece in the HIV-1 Replication Puzzle
title_sort tetraspanins another piece in the hiv 1 replication puzzle
topic tetraspanins
HIV
entry
assembly
budding
reverse transcription
url https://www.frontiersin.org/article/10.3389/fimmu.2018.01811/full
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