Cargando…

Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion

Human T-cell tropic virus type 1 (HTLV-1) is known to be mainly transmitted by cell-to-cell contact due to the lower infectivity of the cell-free virion. However, the reasons why cell-free HTLV-1 infection is poor remain unknown. In this study, we found that the retrovirus pseudotyped with HTLV-1 vi...

Descripción completa

Detalles Bibliográficos
Autores principales: Maeda, Yosuke, Monde, Kazuaki, Terasawa, Hiromi, Tanaka, Yuetsu, Sawa, Tomohiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671467/
https://www.ncbi.nlm.nih.gov/pubmed/38003710
http://dx.doi.org/10.3390/ijms242216520
_version_ 1785149419890409472
author Maeda, Yosuke
Monde, Kazuaki
Terasawa, Hiromi
Tanaka, Yuetsu
Sawa, Tomohiro
author_facet Maeda, Yosuke
Monde, Kazuaki
Terasawa, Hiromi
Tanaka, Yuetsu
Sawa, Tomohiro
author_sort Maeda, Yosuke
collection PubMed
description Human T-cell tropic virus type 1 (HTLV-1) is known to be mainly transmitted by cell-to-cell contact due to the lower infectivity of the cell-free virion. However, the reasons why cell-free HTLV-1 infection is poor remain unknown. In this study, we found that the retrovirus pseudotyped with HTLV-1 viral envelope glycoprotein (Env) was infectious when human immunodeficiency virus type 1 (HIV-1) was used to produce the virus. We found that the incorporation of HTLV-1 Env into virus-like particles (VLPs) was low when HTLV-1 Gag was used to produce VLPs, whereas VLPs produced using HIV-1 Gag efficiently incorporated HTLV-1 Env. The production of VLPs using Gag chimeras between HTLV-1 and HIV-1 Gag and deletion mutants of HIV-1 Gag showed that the p6 domain of HIV-1 Gag was responsible for the efficient incorporation of HTLV-1 Env into the VLPs. Further mutagenic analyses of the p6 domain of HIV-1 Gag revealed that the PTAP motif in the p6 domain of HIV-1 Gag facilitates the incorporation of HTLV-1 Env into VLPs. Since the PTAP motif is known to interact with tumor susceptibility gene 101 (TSG101) during the budding process, we evaluated the effect of TSG101 knockdown on the incorporation of HTLV-1 Env into VLPs. We found that TSG101 knockdown suppressed the incorporation of HTLV-1 Env into VLPs and decreased the infectivity of cell-free HIV-1 pseudotyped with HTLV-1 Env. Our results suggest that the interaction of TSG101 with the PTAP motif of the retroviral L domain is involved not only in the budding process but also in the efficient incorporation of HTLV-1 Env into the cell-free virus.
format Online
Article
Text
id pubmed-10671467
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106714672023-11-20 Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion Maeda, Yosuke Monde, Kazuaki Terasawa, Hiromi Tanaka, Yuetsu Sawa, Tomohiro Int J Mol Sci Article Human T-cell tropic virus type 1 (HTLV-1) is known to be mainly transmitted by cell-to-cell contact due to the lower infectivity of the cell-free virion. However, the reasons why cell-free HTLV-1 infection is poor remain unknown. In this study, we found that the retrovirus pseudotyped with HTLV-1 viral envelope glycoprotein (Env) was infectious when human immunodeficiency virus type 1 (HIV-1) was used to produce the virus. We found that the incorporation of HTLV-1 Env into virus-like particles (VLPs) was low when HTLV-1 Gag was used to produce VLPs, whereas VLPs produced using HIV-1 Gag efficiently incorporated HTLV-1 Env. The production of VLPs using Gag chimeras between HTLV-1 and HIV-1 Gag and deletion mutants of HIV-1 Gag showed that the p6 domain of HIV-1 Gag was responsible for the efficient incorporation of HTLV-1 Env into the VLPs. Further mutagenic analyses of the p6 domain of HIV-1 Gag revealed that the PTAP motif in the p6 domain of HIV-1 Gag facilitates the incorporation of HTLV-1 Env into VLPs. Since the PTAP motif is known to interact with tumor susceptibility gene 101 (TSG101) during the budding process, we evaluated the effect of TSG101 knockdown on the incorporation of HTLV-1 Env into VLPs. We found that TSG101 knockdown suppressed the incorporation of HTLV-1 Env into VLPs and decreased the infectivity of cell-free HIV-1 pseudotyped with HTLV-1 Env. Our results suggest that the interaction of TSG101 with the PTAP motif of the retroviral L domain is involved not only in the budding process but also in the efficient incorporation of HTLV-1 Env into the cell-free virus. MDPI 2023-11-20 /pmc/articles/PMC10671467/ /pubmed/38003710 http://dx.doi.org/10.3390/ijms242216520 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maeda, Yosuke
Monde, Kazuaki
Terasawa, Hiromi
Tanaka, Yuetsu
Sawa, Tomohiro
Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion
title Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion
title_full Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion
title_fullStr Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion
title_full_unstemmed Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion
title_short Interaction of TSG101 with the PTAP Motif in Distinct Locations of Gag Determines the Incorporation of HTLV-1 Env into the Retroviral Virion
title_sort interaction of tsg101 with the ptap motif in distinct locations of gag determines the incorporation of htlv-1 env into the retroviral virion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671467/
https://www.ncbi.nlm.nih.gov/pubmed/38003710
http://dx.doi.org/10.3390/ijms242216520
work_keys_str_mv AT maedayosuke interactionoftsg101withtheptapmotifindistinctlocationsofgagdeterminestheincorporationofhtlv1envintotheretroviralvirion
AT mondekazuaki interactionoftsg101withtheptapmotifindistinctlocationsofgagdeterminestheincorporationofhtlv1envintotheretroviralvirion
AT terasawahiromi interactionoftsg101withtheptapmotifindistinctlocationsofgagdeterminestheincorporationofhtlv1envintotheretroviralvirion
AT tanakayuetsu interactionoftsg101withtheptapmotifindistinctlocationsofgagdeterminestheincorporationofhtlv1envintotheretroviralvirion
AT sawatomohiro interactionoftsg101withtheptapmotifindistinctlocationsofgagdeterminestheincorporationofhtlv1envintotheretroviralvirion