Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.

After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding intera...

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Autores principales:	Sadayuki Ohkura, David C Goldstone, Melvyn W Yap, Kate Holden-Dye, Ian A Taylor, Jonathan P Stoye
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/e14623c8542c4a23b9eb1c9c061eed64
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spelling	oai:doaj.org-article:e14623c8542c4a23b9eb1c9c061eed642021-11-18T06:03:29ZNovel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.1553-73661553-737410.1371/journal.ppat.1002011https://doaj.org/article/e14623c8542c4a23b9eb1c9c061eed642011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21483490/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding interaction between TRIM5α and CA, we selected a panel of novel N-tropic murine leukaemia virus (N-MLV) escape mutants by a serial passage of replication competent N-MLV in rhesus macaque TRIM5α (rhTRIM5α)-positive cells using a small percentage of unrestricted cells to allow multiple rounds of virus replication. The newly identified mutations, many of which involve changes in charge, are distributed over the outer 'top' surface of N-MLV CA, including the N-terminal β-hairpin, and map up to 29 A(o) apart. Biological characterisation with a number of restriction factors revealed that only one of the new mutations affects restriction by human TRIM5α, indicating significant differences in the binding interaction between N-MLV and the two TRIM5αs, whereas three of the mutations result in dual sensitivity to Fv1(n) and Fv1(b). Structural studies of two mutants show that no major changes in the overall CA conformation are associated with escape from restriction. We conclude that interactions involving much, if not all, of the surface of CA are vital for TRIM5α binding.Sadayuki OhkuraDavid C GoldstoneMelvyn W YapKate Holden-DyeIan A TaylorJonathan P StoyePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 3, p e1002011 (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 Sadayuki Ohkura David C Goldstone Melvyn W Yap Kate Holden-Dye Ian A Taylor Jonathan P Stoye Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
description	After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding interaction between TRIM5α and CA, we selected a panel of novel N-tropic murine leukaemia virus (N-MLV) escape mutants by a serial passage of replication competent N-MLV in rhesus macaque TRIM5α (rhTRIM5α)-positive cells using a small percentage of unrestricted cells to allow multiple rounds of virus replication. The newly identified mutations, many of which involve changes in charge, are distributed over the outer 'top' surface of N-MLV CA, including the N-terminal β-hairpin, and map up to 29 A(o) apart. Biological characterisation with a number of restriction factors revealed that only one of the new mutations affects restriction by human TRIM5α, indicating significant differences in the binding interaction between N-MLV and the two TRIM5αs, whereas three of the mutations result in dual sensitivity to Fv1(n) and Fv1(b). Structural studies of two mutants show that no major changes in the overall CA conformation are associated with escape from restriction. We conclude that interactions involving much, if not all, of the surface of CA are vital for TRIM5α binding.
format	article
author	Sadayuki Ohkura David C Goldstone Melvyn W Yap Kate Holden-Dye Ian A Taylor Jonathan P Stoye
author_facet	Sadayuki Ohkura David C Goldstone Melvyn W Yap Kate Holden-Dye Ian A Taylor Jonathan P Stoye
author_sort	Sadayuki Ohkura
title	Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
title_short	Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
title_full	Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
title_fullStr	Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
title_full_unstemmed	Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
title_sort	novel escape mutants suggest an extensive trim5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/e14623c8542c4a23b9eb1c9c061eed64
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Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.

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