SUMO-interacting motifs of human TRIM5α are important for antiviral activity.

Human TRIM5α potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains) but not others (the B- or NB-tropic strains) during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-ML...

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Autores principales:	Gloria Arriagada, Lucia N Muntean, Stephen P Goff
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/05e2f706254c4c9cb81d9b4ab0376e9f
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spelling	oai:doaj.org-article:05e2f706254c4c9cb81d9b4ab0376e9f2021-11-18T06:03:29ZSUMO-interacting motifs of human TRIM5α are important for antiviral activity.1553-73661553-737410.1371/journal.ppat.1002019https://doaj.org/article/05e2f706254c4c9cb81d9b4ab0376e9f2011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21490953/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human TRIM5α potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains) but not others (the B- or NB-tropic strains) during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor the mutant R110E of N-MLV CA (a B-tropic switch) are affected by SUMO-1 overexpression. The block occurred prior to reverse transcription and could be abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral effects, and this loss of restriction could be restored by expression of a human TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and three putative SUMO interacting motifs (SIMs) in the B30.2 domain. Mutations of the TRIM5α consensus SUMO conjugation site did not affect the antiviral activity of TRIM5α in any of the cell types tested. Mutation of the SIM consensus sequences, however, abolished TRIM5α antiviral activity against N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation of CA, are required for restriction. We propose that at least a portion of the antiviral activity of TRIM5α is mediated through the binding of its SIMs to SUMO-conjugated CA.Gloria ArriagadaLucia N MunteanStephen P GoffPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 4, p e1002019 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Gloria Arriagada Lucia N Muntean Stephen P Goff SUMO-interacting motifs of human TRIM5α are important for antiviral activity.
description	Human TRIM5α potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains) but not others (the B- or NB-tropic strains) during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor the mutant R110E of N-MLV CA (a B-tropic switch) are affected by SUMO-1 overexpression. The block occurred prior to reverse transcription and could be abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral effects, and this loss of restriction could be restored by expression of a human TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and three putative SUMO interacting motifs (SIMs) in the B30.2 domain. Mutations of the TRIM5α consensus SUMO conjugation site did not affect the antiviral activity of TRIM5α in any of the cell types tested. Mutation of the SIM consensus sequences, however, abolished TRIM5α antiviral activity against N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation of CA, are required for restriction. We propose that at least a portion of the antiviral activity of TRIM5α is mediated through the binding of its SIMs to SUMO-conjugated CA.
format	article
author	Gloria Arriagada Lucia N Muntean Stephen P Goff
author_facet	Gloria Arriagada Lucia N Muntean Stephen P Goff
author_sort	Gloria Arriagada
title	SUMO-interacting motifs of human TRIM5α are important for antiviral activity.
title_short	SUMO-interacting motifs of human TRIM5α are important for antiviral activity.
title_full	SUMO-interacting motifs of human TRIM5α are important for antiviral activity.
title_fullStr	SUMO-interacting motifs of human TRIM5α are important for antiviral activity.
title_full_unstemmed	SUMO-interacting motifs of human TRIM5α are important for antiviral activity.
title_sort	sumo-interacting motifs of human trim5α are important for antiviral activity.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/05e2f706254c4c9cb81d9b4ab0376e9f
work_keys_str_mv	AT gloriaarriagada sumointeractingmotifsofhumantrim5aareimportantforantiviralactivity AT lucianmuntean sumointeractingmotifsofhumantrim5aareimportantforantiviralactivity AT stephenpgoff sumointeractingmotifsofhumantrim5aareimportantforantiviralactivity
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SUMO-interacting motifs of human TRIM5α are important for antiviral activity.

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