A human TRIM5α B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus

Felipe Diaz-Griffero; Michel Perron; Kathleen McGee-Estrada; Robert Hanna; Pierre V. Maillard; Didier Trono; Joseph Sodroski

doi:10.1016/j.virol.2008.05.008

A human TRIM5α B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus

Felipe Diaz-Griffero, Michel Perron, Kathleen McGee-Estrada, Robert Hanna, Pierre V. Maillard, Didier Trono, Joseph Sodroski

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

60 Scopus citations

Abstract

Human TRIM5α restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5α that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIV_mac and HIV-2 infection. B-MLV and SIV_mac infections were blocked by the mutant TRIM5α proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5α can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid.

Original language	English (US)
Pages (from-to)	233-242
Number of pages	10
Journal	Virology
Volume	378
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2008.05.008
State	Published - Sep 1 2008
Externally published	Yes

Keywords

Capsid
Mechanism
Restriction factor
Retrovirus
Reverse transcription
Tripartite motif
Uncoating

ASJC Scopus subject areas

Virology

UN SDGs

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

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10.1016/j.virol.2008.05.008

Cite this

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title = "A human TRIM5α B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus",

abstract = "Human TRIM5α restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5α that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIVmac and HIV-2 infection. B-MLV and SIVmac infections were blocked by the mutant TRIM5α proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5α can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid.",

keywords = "Capsid, Mechanism, Restriction factor, Retrovirus, Reverse transcription, Tripartite motif, Uncoating",

author = "Felipe Diaz-Griffero and Michel Perron and Kathleen McGee-Estrada and Robert Hanna and Maillard, {Pierre V.} and Didier Trono and Joseph Sodroski",

note = "Funding Information: We thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for the manuscript preparation, Drs. Gregory Towers, Jeremy Luban and Andrew Lever for providing recombinant HIV-2, and the National Institutes of Health (AI063987, AI076094 and a Center for AIDS Research Award AI60354), the International AIDS Vaccine Initiative, the Bristol-Myers Squibb Foundation, the Swiss National Science Foundation, and the late William F. McCarty-Cooper for research funding. F.D.-G. was the recipient of an amfAR Mathilde Krim Fellowship in Basic Biomedical Research.",

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doi = "10.1016/j.virol.2008.05.008",

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T1 - A human TRIM5α B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus

AU - Diaz-Griffero, Felipe

AU - Perron, Michel

AU - McGee-Estrada, Kathleen

AU - Hanna, Robert

AU - Maillard, Pierre V.

AU - Trono, Didier

AU - Sodroski, Joseph

N1 - Funding Information: We thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for the manuscript preparation, Drs. Gregory Towers, Jeremy Luban and Andrew Lever for providing recombinant HIV-2, and the National Institutes of Health (AI063987, AI076094 and a Center for AIDS Research Award AI60354), the International AIDS Vaccine Initiative, the Bristol-Myers Squibb Foundation, the Swiss National Science Foundation, and the late William F. McCarty-Cooper for research funding. F.D.-G. was the recipient of an amfAR Mathilde Krim Fellowship in Basic Biomedical Research.

PY - 2008/9/1

Y1 - 2008/9/1

N2 - Human TRIM5α restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5α that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIVmac and HIV-2 infection. B-MLV and SIVmac infections were blocked by the mutant TRIM5α proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5α can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid.

AB - Human TRIM5α restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5α that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIVmac and HIV-2 infection. B-MLV and SIVmac infections were blocked by the mutant TRIM5α proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5α can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid.

KW - Capsid

KW - Mechanism

KW - Restriction factor

KW - Retrovirus

KW - Reverse transcription

KW - Tripartite motif

KW - Uncoating

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A human TRIM5α B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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