Evolution of HIV-1 envelope sequences and coreceptor tropism during pregnancy
Notice bibliographique
Résumé
HIV-1 Env mediates viral entry into target cells and defines R5 or X4 phenotype. HIV tropism is important in pathogenesis and is associated with mother-to-child transmission. Env is under strong selective pressure within the host. The aim of this study was to determine whether changes in maternal immunity associated with initiation and progression of pregnancy influence Env sequence variation and HIV-1 coreceptor usage. A longitudinal study of Env sequence variation was performed in 25 pregnant women infected with HIV-1 of clade B (n = 16) or non-B (n = 9). Viral RNA was extracted from plasma, the env gene (nucleotide positions 6430–7374) was PCR-amplified and subcloned, and a mean of 20 clones were sequenced per trimester of pregnancy. HIV tropism was predicted in silico using PSSM X4R5 , PSSM SINSI , SVM, geno2pheno and charge rule algorithms. Phylogenetic reconstructions were built, sequence diversity was estimated using p distances and selective pressure (dN/dS) was computed. In study subjects, HIV-1 viral load decreased progressively during the course of pregnancy. Envelope sequences were amplified at all trimesters in 63% of the cases. Phylogenetic analysis revealed at least partial clustering of sequences per trimester in 4 out of 9 patients. Nucleic acid p distances were negatively correlated with CD4 T cell counts at study entry (r = 0.66, p = 0.02). In all clade B variants examined, R5 phenotype was predicted by all algorithms. Interestingly, while predictions were not as consistent with non-B subtypes, R5 and X4 variants were shown to coexist during pregnancy in 4 of 5 cases. Of note, evolution of tropism from R5 to X4 was observed in one subject, and evolution from dual tropism to exclusive X4 was observed in another subject between two consecutive pregnancies. Higher levels of genetic diversity in the V2 region were observed in subjects infected with non-B subtypes as compared with clade B variants. Finally, selective pressure on V2 tended to decrease with time in subjects infected with the B subtype but remained relatively high in sequences derived from carriers of non-B subtypes. This study provides insights into the possible interplay between viral population dynamics and selective pressures exerted by maternal HIV-1 specific immune response during pregnancy, insights that could prove invaluable for the development of active and/or passive immunization strategies to prevent mother-to-child transmission of HIV-1.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».