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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.

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.

SUBMITTER: Han C

PROVIDER: S-EPMC7373194 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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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.

Han Changze C Johnson Jacklyn J Dong Rentian R Kandula Raghavendranath R Kort Alexa A Wong Maria M Yang Tianbao T Breheny Patrick J PJ Brown Grant D GD Haim Hillel H

mBio 20200609 3

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 o ...[more]

PMID: 32518179

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Project description:BackgroundA recent clinical trial showed that an immediate transition to very low nicotine content (VLNC) cigarettes, compared with a gradual transition, produced greater reductions in smoking behavior, smoke exposure, and dependence. However, there was less compliance with the instruction to smoke only VLNC cigarettes in the immediate versus gradual reduction condition. The goal of this study was to test whether nicotine reduction method alters subjective ratings of VLNC cigarettes, and whether subjective ratings mediate effects of nicotine reduction method on smoking behavior, smoke exposure, dependence, and compliance.MethodsThis is a secondary analysis of a randomized trial conducted across 10 sites in the United States. Smokers (n = 1250) were randomized to either a control condition, or to have the nicotine content of their cigarettes reduced immediately or gradually to 0.04 mg nicotine/g of tobacco during a 20-week study period. Participants completed the modified Cigarette Evaluation Questionnaire (mCEQ).ResultsAfter Week 20, the immediate reduction group scored significantly lower than the gradual reduction group on multiple subscales of the mCEQ (ps < .001). The Satisfaction subscale of the mCEQ mediated the impact of nicotine reduction method on smoke exposure, smoking behavior, dependence, compliance, and abstinence. Other subscales also mediated a subset of these outcomes.ConclusionsAn immediate reduction in nicotine content resulted in lower product satisfaction than a gradual reduction, suggesting that immediate reduction further reduces cigarette reward value. This study will provide the Food and Drug Administration with information about the impact of nicotine reduction method on cigarette reward value.ImplicationsThese data suggest that an immediate reduction in nicotine content will result in greater reductions in cigarette satisfaction than a gradual reduction, and this reduction in satisfaction is related to changes in smoking behavior and dependence.

Dataset Information

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

Publications

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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