Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies

Louie, Raymond H. Y.; Kaczorowski, Kevin J.; Barton, John P.; Chakraborty, Arup K.; McKay, Matthew R.

doi:10.1073/pnas.1717765115

Cited by 115 publications

(156 citation statements)

References 66 publications

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“…Research efforts directed towards the design and development of vaccines for SARS-CoV-2 are increasing, and some related analyses are already being reported in distinct, parallel studies. These studies, like our own, are based on leveraging available data and computational methods, and add to recent work focused on computational analysis and design of vaccines for various different viruses (e.g., [49][50][51][52][53][54]. A preliminary analysis of linear SARS-CoV-derived B cell epitopes has been reported online on the ViPR database website (https://www.viprbrc.org/brcDocs/documents/announcements/ Corona/2019-nCoV-ViPR-report_24JAN2020.pdf).…”

Section: Discussionmentioning

confidence: 95%

Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Ahmed

Quadeer

McKay

2020

Viruses

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1,058

899

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A.A.Q); m.mckay@ust.hk (M.R.M.) † These authors contributed equally to this work.Abstract: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

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Section: Discussionmentioning

confidence: 95%

Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Ahmed

Quadeer

McKay

2020

Viruses

Self Cite

1,058

899

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“…Complicating this idea is the fact that selection operates at different levels [30,40], which shapes HIV-1's fitness landscape in a non-trivial manner. Recently, the characteristics of this fitness landscape itself have become a subject of study, wherein the Ising model is used to map HIV genomes to (proxies of) fitness [5,27,41,48,52]. In addition, the environment (i.e.…”

Section: Introductionmentioning

confidence: 99%

Modeling the immunological pre-adaptation of HIV-1

Dorp

Boven

Boer³

2020

Preprint

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It is becoming increasingly evident that the evolution of HIV-1 is to a large extent determined by the immunological background of the host. On the population-level this results in associations between specific human leukocyte antigen (HLA) alleles and polymorphic loci of the virus. Furthermore, some HLA alleles that were previously associated with slow progression to AIDS have been shown to lose their protective effect, because HLA-specific immunological escape variants have spread through the population. This phenomenon is known as immunological preadaptation. Apart from adapting to human immune responses, the set-point virus load (SPVL) of HIV-1 is thought to have evolved to values that optimize the population-level fitness of the virus. This suggestion is supported by considerable heritability of the SPVL. Previous modeling studies show that whether or not SPVL optimization is expected to occur depends sensitively on the underlying assumptions with respect to the extent of within-versus between-host selection. Here we use a detailed and semi-realistic multi-level HIV-1 model in which immunological preadaptation and SPVL evolution can emerge from the underlying interactions of the virus with the immune system of the host. This enables us to study the effect of immunological escape on disease progression, and how disease progression may be molded by SPVL evolution. We find that the time to AIDS could decrease significantly (0.5-1.0 years) in a HLA-dependent manner by immunological pre-adaptation over the long-term course of the epidemic (> 100 years). We find that SPVL is not expected to evolve to optimize the population-level fitness of HIV-1, even though high heritability of the SPVL emerges from continual selection of immune-escape mutations.

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“…It is important to note that it is not necessary for the focal lineages to belong to well separated clades to be suitable for our test, unlike some other methods (Tamuri et al 2009). Moreover, our method makes no assumption regarding model of epistatic interactions or fitness shift (Tamuri et al 2009;Louie et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic inference of changes in amino acid propensities with single-position resolution

Klink

Kalinina

Bazykin

2019

Preprint

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Fitness conferred by the same allele may differ between genotypes, and these differences shape variation and evolution. Changes in amino acid propensities at protein sites over the course of evolution have been inferred from sequence alignments statistically, but the existing methods are data-intensive and aggregate multiple sites. Here, we develop an approach to detect individual amino acids that confer different fitness in different groups of species from combined sequence and phylogenetic data. Our method is based on the mutual distribution of homoplasic (convergent or parallel) and divergent substitutions over a phylogeny, and uses the fact that a higher rate of homoplasic evolution within a clade signifies high fitness of the derived allele. We apply it to the env gene of two HIV-1 subtypes, A and B, and to the HA gene of two influenza A subtypes, H1 and H3, and show that the inferred fitness changes are consistent with the fitness differences observed in deep mutational scanning experiments. Changes in fitness do not always trigger episodes of positive selection, and therefore cannot be identified by existing methods for its detection.

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Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies

Cited by 115 publications

References 66 publications

Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Modeling the immunological pre-adaptation of HIV-1

Phylogenetic inference of changes in amino acid propensities with single-position resolution

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