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Record W4317715921 · doi:10.1101/2023.01.21.525033

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting

2023· preprint· en· W4317715921 on OpenAlexaff
Manukumar Honnayakanahalli Marichannegowda, Michelle Zemil, Lindsay Wieczorek, Eric Sanders‐Buell, Meera Bose, Anne Marie O’Sullivan, David B. King, Leilani Francisco, Felisa Diaz‐Mendez, Saini Setua, Nicolas Chomont, Nittaya Phanuphak, Jintanat Ananworanich, Denise C. Hsu, Sandhya Vasan, Nelson L. Michael, Leigh Anne Eller, Sodsai Tovanabutra, Yutaka Tagaya, Merlin L. Robb, Victoria R. Polonis, Hongshuo Song

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsCentre Hospitalier de l’Université de Montréal
FundersU.S. Army Medical Research and Development CommandNational Institute of Allergy and Infectious DiseasesNational Institutes of HealthU.S. ArmyU.S. Department of DefenseGilead SciencesViiV HealthcareHenry M. Jackson Foundation
KeywordsTropismBiologyVirologyAntigenicityTissue tropismHuman immunodeficiency virus (HIV)CXCR4MutationVirusImmune systemGeneticsGeneAntigenChemokine

Abstract

fetched live from OpenAlex

Abstract The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the underlying mechanisms remain unclear. The difficulty in capturing the earliest moment of coreceptor switch in vivo limits our understanding of this phenomenon. Here, by tracking the evolution of the transmitted/founder (T/F) HIV-1 in a prospective cohort of individuals at risk for HIV-1 infection identified very early in acute infection, we investigated this process with high resolution. The earliest X4 variants evolved from the R5 tropic T/F strains. Strong X4 usage can be conferred by a single mutation. The mutations responsible for coreceptor switch can confer escape to neutralization and drive X4 variants to replicate mainly in the central memory and naïve CD4+ T cells. We propose a novel concept to explain the co-evolution of virus antigenicity and entry tropism termed “escape by shifting”. This concept posits that for viruses with receptor or coreceptor flexibility, entry tropism alteration represents a mechanism of immune evasion in vivo .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.246
Teacher spread0.225 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2023
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicHIV Research and Treatment→French-language works237,207→