Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication

Gag proteins underlie retroviral replication by fulfilling numerous functional roles at various stages during viral life cycle. Out of the four mature proteins, Gag-capsid (CA) is a major component of viral particles, and has been most well studied biogenetically, biochemically and structurally. Gag...

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Main Authors: Naoya Doi, Takaaki Koma, Akio Adachi, Masako Nomaguchi
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-08-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2019.01831/full
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author Naoya Doi
Takaaki Koma
Akio Adachi
Masako Nomaguchi
author_facet Naoya Doi
Takaaki Koma
Akio Adachi
Masako Nomaguchi
author_sort Naoya Doi
collection DOAJ
description Gag proteins underlie retroviral replication by fulfilling numerous functional roles at various stages during viral life cycle. Out of the four mature proteins, Gag-capsid (CA) is a major component of viral particles, and has been most well studied biogenetically, biochemically and structurally. Gag-CA is composed of two structured domains, and also of a short stretch of disordered and flexible interdomain linker. While the two domains, namely, N-terminal and C-terminal domains (NTD and CTD), have been the central target for Gag research, the linker region connecting the two has been poorly studied. We recently have performed systemic mutational analyses on the Gag-CA linker region of HIV-1 by various experimental and in silico systems. In total, we have demonstrated that the linker region acts as a cis-modulator to optimize the Gag-related viral replication process. We also have noted, during the course of conducting the research project, that HIV-1 and SIVmac, belonging to distinct primate lentiviral lineages, share a similarly biologically active linker region with each other. In this brief article, we summarize and report the results obtained by mutational studies that are relevant to the functional significance of the interdomain linker of HIV/SIV Gag-CA. Based on this investigation, we discuss about the future directions of the research in this line.
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spelling doaj.art-f86df23e18ed4f32be960050d556af532022-12-22T00:02:37ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-08-011010.3389/fmicb.2019.01831479908Role for Gag-CA Interdomain Linker in Primate Lentiviral ReplicationNaoya Doi0Takaaki Koma1Akio Adachi2Masako Nomaguchi3Department of Microbiology, Graduate School of Medical Science, Tokushima University, Tokushima, JapanDepartment of Microbiology, Graduate School of Medical Science, Tokushima University, Tokushima, JapanDepartment of Microbiology, Kansai Medical University, Osaka, JapanDepartment of Microbiology, Graduate School of Medical Science, Tokushima University, Tokushima, JapanGag proteins underlie retroviral replication by fulfilling numerous functional roles at various stages during viral life cycle. Out of the four mature proteins, Gag-capsid (CA) is a major component of viral particles, and has been most well studied biogenetically, biochemically and structurally. Gag-CA is composed of two structured domains, and also of a short stretch of disordered and flexible interdomain linker. While the two domains, namely, N-terminal and C-terminal domains (NTD and CTD), have been the central target for Gag research, the linker region connecting the two has been poorly studied. We recently have performed systemic mutational analyses on the Gag-CA linker region of HIV-1 by various experimental and in silico systems. In total, we have demonstrated that the linker region acts as a cis-modulator to optimize the Gag-related viral replication process. We also have noted, during the course of conducting the research project, that HIV-1 and SIVmac, belonging to distinct primate lentiviral lineages, share a similarly biologically active linker region with each other. In this brief article, we summarize and report the results obtained by mutational studies that are relevant to the functional significance of the interdomain linker of HIV/SIV Gag-CA. Based on this investigation, we discuss about the future directions of the research in this line.https://www.frontiersin.org/article/10.3389/fmicb.2019.01831/fullHIV/SIVGag-CAinterdomain linkerGag assemblyvirus productionearly infectivity
spellingShingle Naoya Doi
Takaaki Koma
Akio Adachi
Masako Nomaguchi
Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication
Frontiers in Microbiology
HIV/SIV
Gag-CA
interdomain linker
Gag assembly
virus production
early infectivity
title Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication
title_full Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication
title_fullStr Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication
title_full_unstemmed Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication
title_short Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication
title_sort role for gag ca interdomain linker in primate lentiviral replication
topic HIV/SIV
Gag-CA
interdomain linker
Gag assembly
virus production
early infectivity
url https://www.frontiersin.org/article/10.3389/fmicb.2019.01831/full
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AT takaakikoma roleforgagcainterdomainlinkerinprimatelentiviralreplication
AT akioadachi roleforgagcainterdomainlinkerinprimatelentiviralreplication
AT masakonomaguchi roleforgagcainterdomainlinkerinprimatelentiviralreplication