Evidence map›Paper›PMID 23468626›Full record

ArticlePLoS pathogens2013

Increased functional stability and homogeneity of viral envelope spikes through directed evolution.

Daniel P Leaman, Michael B Zwick

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 50 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Daniel P LeamanDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
Michael B Zwick
Scripps Research Institute · US

Funding

INTERDISCIPLINARY TRAINING PROGRAM IN IMMUNOLOGYT32AI007606 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 1999 to 2013
$2.1M
Engineering and sorting HIV-1 display Env libraries for vaccine designR33AI077381 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ZWICK, MICHAEL B · 2011 to 2013
$1.7M
NIAID NIH HHS R01 AI06993NIAID NIH HHS R33 AI077381NIAID NIH HHS T32 AI007606
6 · The paper itself

Abstract

The functional HIV-1 envelope glycoprotein (Env) trimer, the target of anti-HIV-1 neutralizing antibodies (Abs), is innately labile and coexists with non-native forms of Env. This lability and heterogeneity in Env has been associated with its tendency to elicit non-neutralizing Abs. Here, we use directed evolution to overcome instability and heterogeneity of a primary Env spike. HIV-1 virions were subjected to iterative cycles of destabilization followed by replication to select for Envs with enhanced stability. Two separate pools of stable Env variants with distinct sequence changes were selected using this method. Clones isolated from these viral pools could withstand heat, denaturants and other destabilizing conditions. Seven mutations in Env were associated with increased trimer stability, primarily in the heptad repeat regions of gp41, but also in V1 of gp120. Combining the seven mutations generated a variant Env with superior homogeneity and stability. This variant spike moreover showed resistance to proteolysis and to dissociation by detergent. Heterogeneity within the functional population of hyper-stable Envs was also reduced, as evidenced by a relative decrease in a proportion of virus that is resistant to the neutralizing Ab, PG9. The latter result may reflect a change in glycans on the stabilized Envs. The stabilizing mutations also increased the proportion of secreted gp140 existing in a trimeric conformation. Finally, several Env-stabilizing substitutions could stabilize Env spikes from HIV-1 clades A, B and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure.

Indexed as

Directed Molecular EvolutionAntibodies, ViralCell LineCloning, Molecularenv Gene Products, Human Immunodeficiency VirusHIV-1HIV Envelope Protein gp120HumansMutationProtein DenaturationUreaVirionAntibodies, Viralenv Gene Products, Human Immunodeficiency VirusHIV Envelope Protein gp120Urea

Identifiers

PMID23468626
PMCPMC3585149
OpenAlexW2053369698

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.