Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis

Yusuke Matsui; Keisuke Shindo; Kayoko Nagata; Katsuhiro Io; Kohei Tada; Fumie Iwai; Masayuki Kobayashi; Norimitsu Kadowaki; Reuben S. Harris; Akifumi Takaori-Kondo

doi:10.1016/j.virol.2013.11.004

Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis

Yusuke Matsui
, Keisuke Shindo
, Kayoko Nagata
, Katsuhiro Io
, Kohei Tada
, Fumie Iwai
, Masayuki Kobayashi
, Norimitsu Kadowaki
, Reuben S. Harris
, Akifumi Takaori-Kondo

Molecular Biology (BMBB)

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Vif is essential for HIV-1 replication in T cells and macrophages. Vif recruits a host ubiquitin ligase complex to promote proteasomal degradation of the APOBEC3 restriction factors by poly-ubiquitination. The cellular transcription cofactor CBFβ is required for Vif function by stabilizing the Vif protein and promoting recruitment of a cellular Cullin5-RING ubiquitin ligase complex. Interaction between Vif and CBFβ is a promising therapeutic target, but little is known about the interfacial residues. We now demonstrate that Vif conserved residues E88/W89 are crucial for CBFβ binding. Substitution of E88/W89 to alanines impaired binding to CBFβ, degradation of APOBEC3, and virus infectivity in the presence of APOBEC3 in single-cycle infection. In spreading infection, NL4-3 with Vif E88A/W89A mutation replicated comparably to wild-type virus in permissive CEM-SS cells, but not in multiple APOBEC3 expressing non-permissive CEM cells. These results support a model in which HIV-1 Vif residues E88/W89 may participate in binding CBFβ.

Original language	English (US)
Pages (from-to)	82-87
Number of pages	6
Journal	Virology
Volume	449
DOIs	https://doi.org/10.1016/j.virol.2013.11.004
State	Published - Jan 20 2014

Bibliographical note

Funding Information:
This study was partly supported by Grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology and from the Ministry of Health, Labor and Welfare in Japan . Work in the Harris lab was supported in part by grants from the National Institutes of Health ( R01 AI064046 and P01 GM091743).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CBFβ
HIV-1
Host factors
Interaction
Vif

Publisher link

10.1016/j.virol.2013.11.004

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title = "Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis",

abstract = "Vif is essential for HIV-1 replication in T cells and macrophages. Vif recruits a host ubiquitin ligase complex to promote proteasomal degradation of the APOBEC3 restriction factors by poly-ubiquitination. The cellular transcription cofactor CBFβ is required for Vif function by stabilizing the Vif protein and promoting recruitment of a cellular Cullin5-RING ubiquitin ligase complex. Interaction between Vif and CBFβ is a promising therapeutic target, but little is known about the interfacial residues. We now demonstrate that Vif conserved residues E88/W89 are crucial for CBFβ binding. Substitution of E88/W89 to alanines impaired binding to CBFβ, degradation of APOBEC3, and virus infectivity in the presence of APOBEC3 in single-cycle infection. In spreading infection, NL4-3 with Vif E88A/W89A mutation replicated comparably to wild-type virus in permissive CEM-SS cells, but not in multiple APOBEC3 expressing non-permissive CEM cells. These results support a model in which HIV-1 Vif residues E88/W89 may participate in binding CBFβ.",

keywords = "CBFβ, HIV-1, Host factors, Interaction, Vif",

author = "Yusuke Matsui and Keisuke Shindo and Kayoko Nagata and Katsuhiro Io and Kohei Tada and Fumie Iwai and Masayuki Kobayashi and Norimitsu Kadowaki and Harris, \{Reuben S.\} and Akifumi Takaori-Kondo",

note = "Funding Information: This study was partly supported by Grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology and from the Ministry of Health, Labor and Welfare in Japan . Work in the Harris lab was supported in part by grants from the National Institutes of Health ( R01 AI064046 and P01 GM091743). ",

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doi = "10.1016/j.virol.2013.11.004",

language = "English (US)",

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T1 - Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis

AU - Matsui, Yusuke

AU - Shindo, Keisuke

AU - Nagata, Kayoko

AU - Io, Katsuhiro

AU - Tada, Kohei

AU - Iwai, Fumie

AU - Kobayashi, Masayuki

AU - Kadowaki, Norimitsu

AU - Harris, Reuben S.

AU - Takaori-Kondo, Akifumi

N1 - Funding Information: This study was partly supported by Grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology and from the Ministry of Health, Labor and Welfare in Japan . Work in the Harris lab was supported in part by grants from the National Institutes of Health ( R01 AI064046 and P01 GM091743).

PY - 2014/1/20

Y1 - 2014/1/20

N2 - Vif is essential for HIV-1 replication in T cells and macrophages. Vif recruits a host ubiquitin ligase complex to promote proteasomal degradation of the APOBEC3 restriction factors by poly-ubiquitination. The cellular transcription cofactor CBFβ is required for Vif function by stabilizing the Vif protein and promoting recruitment of a cellular Cullin5-RING ubiquitin ligase complex. Interaction between Vif and CBFβ is a promising therapeutic target, but little is known about the interfacial residues. We now demonstrate that Vif conserved residues E88/W89 are crucial for CBFβ binding. Substitution of E88/W89 to alanines impaired binding to CBFβ, degradation of APOBEC3, and virus infectivity in the presence of APOBEC3 in single-cycle infection. In spreading infection, NL4-3 with Vif E88A/W89A mutation replicated comparably to wild-type virus in permissive CEM-SS cells, but not in multiple APOBEC3 expressing non-permissive CEM cells. These results support a model in which HIV-1 Vif residues E88/W89 may participate in binding CBFβ.

AB - Vif is essential for HIV-1 replication in T cells and macrophages. Vif recruits a host ubiquitin ligase complex to promote proteasomal degradation of the APOBEC3 restriction factors by poly-ubiquitination. The cellular transcription cofactor CBFβ is required for Vif function by stabilizing the Vif protein and promoting recruitment of a cellular Cullin5-RING ubiquitin ligase complex. Interaction between Vif and CBFβ is a promising therapeutic target, but little is known about the interfacial residues. We now demonstrate that Vif conserved residues E88/W89 are crucial for CBFβ binding. Substitution of E88/W89 to alanines impaired binding to CBFβ, degradation of APOBEC3, and virus infectivity in the presence of APOBEC3 in single-cycle infection. In spreading infection, NL4-3 with Vif E88A/W89A mutation replicated comparably to wild-type virus in permissive CEM-SS cells, but not in multiple APOBEC3 expressing non-permissive CEM cells. These results support a model in which HIV-1 Vif residues E88/W89 may participate in binding CBFβ.

KW - CBFβ

KW - HIV-1

KW - Host factors

KW - Interaction

KW - Vif

UR - https://www.scopus.com/pages/publications/84888261024

UR - https://www.scopus.com/pages/publications/84888261024#tab=citedBy

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DO - 10.1016/j.virol.2013.11.004

M3 - Article

C2 - 24418540

AN - SCOPUS:84888261024

SN - 0042-6822

VL - 449

SP - 82

EP - 87

JO - Virology

JF - Virology

ER -

Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis

Abstract

Bibliographical note

UN SDGs

Keywords

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