Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels

ABSTRACT HIV-1 group M was transmitted to humans nearly one century ago. The virus has since evolved to form distinct clades, which spread to different regions of the world. The envelope glycoproteins (Envs) of HIV-1 have rapidly diversified in all infected populations. We examined whether key antig...

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Autores principales:	Changze Han, Jacklyn Johnson, Rentian Dong, Raghavendranath Kandula, Alexa Kort, Maria Wong, Tianbao Yang, Patrick J. Breheny, Grant D. Brown, Hillel Haim
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	HIV-1 envelope glycoproteins population-level evolution vaccine design virus diversity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fe643beff6824ed7bea672931542a0f5
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spelling	oai:doaj.org-article:fe643beff6824ed7bea672931542a0f52021-11-15T15:56:46ZKey Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels10.1128/mBio.00126-202150-7511https://doaj.org/article/fe643beff6824ed7bea672931542a0f52020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00126-20https://doaj.org/toc/2150-7511ABSTRACT HIV-1 group M was transmitted to humans nearly one century ago. The virus has since evolved to form distinct clades, which spread to different regions of the world. The envelope glycoproteins (Envs) of HIV-1 have rapidly diversified in all infected populations. We examined whether key antigenic sites of Env and signatures of vaccine efficacy are evolving toward similar or distinct structural forms in different populations worldwide. Patterns of amino acid variants that emerged at each position of Env were compared between diverse HIV-1 clades and isolates from different geographic regions. Interestingly, at each Env position, the amino acid in the clade ancestral or regional-founder virus was replaced by a unique frequency distribution (FD) of amino acids. FDs are highly conserved in populations from different regions worldwide and in paraphyletic and monophyletic subclade groups. Remarkably, founder effects of Env mutations at the clade and regional levels have gradually decreased during the pandemic by evolution of each site toward the unique combination of variants. Therefore, HIV-1 Env is evolving at a population level toward well-defined “target” states; these states are not specific amino acids but rather specific distributions of amino acid frequencies. Our findings reveal the powerful nature of the forces that guide evolution of Env and their conservation across different populations. Such forces have caused a gradual decrease in the interpopulation diversity of Env despite an increasing intrapopulation diversity. IMPORTANCE The Env protein of HIV-1 is the primary target in AIDS vaccine design. Frequent mutations in the virus increase the number of Env forms in each population, limiting the efficacy of AIDS vaccines. Comparison of newly emerging forms in different populations showed that each position of Env is evolving toward a specific combination of amino acids. Similar changes are occurring in different HIV-1 subtypes and geographic regions toward the same position-specific combinations of amino acids, often from distinct ancestral sequences. The predictable nature of HIV-1 Env evolution, as shown here, provides a new framework for designing vaccines that are tailored to the unique combination of variants expected to emerge in each virus subtype and geographic region.Changze HanJacklyn JohnsonRentian DongRaghavendranath KandulaAlexa KortMaria WongTianbao YangPatrick J. BrehenyGrant D. BrownHillel HaimAmerican Society for MicrobiologyarticleHIV-1envelope glycoproteinspopulation-level evolutionvaccine designvirus diversityMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV-1 envelope glycoproteins population-level evolution vaccine design virus diversity Microbiology QR1-502
spellingShingle	HIV-1 envelope glycoproteins population-level evolution vaccine design virus diversity Microbiology QR1-502 Changze Han Jacklyn Johnson Rentian Dong Raghavendranath Kandula Alexa Kort Maria Wong Tianbao Yang Patrick J. Breheny Grant D. Brown Hillel Haim Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels
description	ABSTRACT HIV-1 group M was transmitted to humans nearly one century ago. The virus has since evolved to form distinct clades, which spread to different regions of the world. The envelope glycoproteins (Envs) of HIV-1 have rapidly diversified in all infected populations. We examined whether key antigenic sites of Env and signatures of vaccine efficacy are evolving toward similar or distinct structural forms in different populations worldwide. Patterns of amino acid variants that emerged at each position of Env were compared between diverse HIV-1 clades and isolates from different geographic regions. Interestingly, at each Env position, the amino acid in the clade ancestral or regional-founder virus was replaced by a unique frequency distribution (FD) of amino acids. FDs are highly conserved in populations from different regions worldwide and in paraphyletic and monophyletic subclade groups. Remarkably, founder effects of Env mutations at the clade and regional levels have gradually decreased during the pandemic by evolution of each site toward the unique combination of variants. Therefore, HIV-1 Env is evolving at a population level toward well-defined “target” states; these states are not specific amino acids but rather specific distributions of amino acid frequencies. Our findings reveal the powerful nature of the forces that guide evolution of Env and their conservation across different populations. Such forces have caused a gradual decrease in the interpopulation diversity of Env despite an increasing intrapopulation diversity. IMPORTANCE The Env protein of HIV-1 is the primary target in AIDS vaccine design. Frequent mutations in the virus increase the number of Env forms in each population, limiting the efficacy of AIDS vaccines. Comparison of newly emerging forms in different populations showed that each position of Env is evolving toward a specific combination of amino acids. Similar changes are occurring in different HIV-1 subtypes and geographic regions toward the same position-specific combinations of amino acids, often from distinct ancestral sequences. The predictable nature of HIV-1 Env evolution, as shown here, provides a new framework for designing vaccines that are tailored to the unique combination of variants expected to emerge in each virus subtype and geographic region.
format	article
author	Changze Han Jacklyn Johnson Rentian Dong Raghavendranath Kandula Alexa Kort Maria Wong Tianbao Yang Patrick J. Breheny Grant D. Brown Hillel Haim
author_facet	Changze Han Jacklyn Johnson Rentian Dong Raghavendranath Kandula Alexa Kort Maria Wong Tianbao Yang Patrick J. Breheny Grant D. Brown Hillel Haim
author_sort	Changze Han
title	Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels
title_short	Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels
title_full	Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels
title_fullStr	Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels
title_full_unstemmed	Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels
title_sort	key positions of hiv-1 env and signatures of vaccine efficacy show gradual reduction of population founder effects at the clade and regional levels
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/fe643beff6824ed7bea672931542a0f5
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Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels

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