Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.

The HIV-1 envelope glycoprotein (Env) gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR) of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-...

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Autores principales:	Lijun Chao, Lu Lu, Hengwen Yang, Yun Zhu, Yuan Li, Qian Wang, Xiaowen Yu, Shibo Jiang, Ying-Hua Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/38acfc20e6dd4a0b8b6327afdb6dc447
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spelling	oai:doaj.org-article:38acfc20e6dd4a0b8b6327afdb6dc4472021-11-18T07:43:19ZIdentification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.1932-620310.1371/journal.pone.0066156https://doaj.org/article/38acfc20e6dd4a0b8b6327afdb6dc4472013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23741527/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The HIV-1 envelope glycoprotein (Env) gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR) of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no, immunogenicity to humans. Here, we found that the C-terminal fragment (aa 462-521) of the human POB1 (the partner of RalBP1), designated C60, is an HIV-1 fusion inhibitor. It bound to N36, the peptide derived from the N-terminal heptad repeat (NHR) of gp41, and to the six-helix bundle (6-HB) formed by N36 and C34, a CHR-peptide, but it did not bind to C34. Unlike the CHR-peptides, C60 did not block gp41 6-HB formation. Rather, results suggest that C60 inhibits HIV-1 fusion by binding to the 6-HB, in particular, the residues in the gp41 NHR domain that are exposed on the surface of 6-HB. Since 6-HB plays a crucial role in the late stage of fusion between the viral envelope and endosomal membrane during the endocytic process of HIV-1, C60 may serve as a host restriction factor to suppress HIV-1 entry into CD4+ T lymphocytes. Taken together, it can be concluded from these results that C60 can be used as a lead for the development of anti-HIV-1 therapeutics or microbicides for the treatment and prevention of HIV-1 infection, as well as a molecular probe to study the fusogenic mechanism of HIV-1.Lijun ChaoLu LuHengwen YangYun ZhuYuan LiQian WangXiaowen YuShibo JiangYing-Hua ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e66156 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lijun Chao Lu Lu Hengwen Yang Yun Zhu Yuan Li Qian Wang Xiaowen Yu Shibo Jiang Ying-Hua Chen Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.
description	The HIV-1 envelope glycoprotein (Env) gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR) of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no, immunogenicity to humans. Here, we found that the C-terminal fragment (aa 462-521) of the human POB1 (the partner of RalBP1), designated C60, is an HIV-1 fusion inhibitor. It bound to N36, the peptide derived from the N-terminal heptad repeat (NHR) of gp41, and to the six-helix bundle (6-HB) formed by N36 and C34, a CHR-peptide, but it did not bind to C34. Unlike the CHR-peptides, C60 did not block gp41 6-HB formation. Rather, results suggest that C60 inhibits HIV-1 fusion by binding to the 6-HB, in particular, the residues in the gp41 NHR domain that are exposed on the surface of 6-HB. Since 6-HB plays a crucial role in the late stage of fusion between the viral envelope and endosomal membrane during the endocytic process of HIV-1, C60 may serve as a host restriction factor to suppress HIV-1 entry into CD4+ T lymphocytes. Taken together, it can be concluded from these results that C60 can be used as a lead for the development of anti-HIV-1 therapeutics or microbicides for the treatment and prevention of HIV-1 infection, as well as a molecular probe to study the fusogenic mechanism of HIV-1.
format	article
author	Lijun Chao Lu Lu Hengwen Yang Yun Zhu Yuan Li Qian Wang Xiaowen Yu Shibo Jiang Ying-Hua Chen
author_facet	Lijun Chao Lu Lu Hengwen Yang Yun Zhu Yuan Li Qian Wang Xiaowen Yu Shibo Jiang Ying-Hua Chen
author_sort	Lijun Chao
title	Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.
title_short	Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.
title_full	Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.
title_fullStr	Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.
title_full_unstemmed	Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.
title_sort	identification of a human protein-derived hiv-1 fusion inhibitor targeting the gp41 fusion core structure.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/38acfc20e6dd4a0b8b6327afdb6dc447
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Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.

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