| Title: |
Diversity of the Nucleic Acid Forms of Circulating HBV in Chronically Infected Patients and Its Impact on Viral Cycle |
| Authors: |
Sotty, Jules; Bablon, Pierre; Lekbaby, Bouchra; Augustin, Jérémy; Girier-Dufournier, Morgane; Langlois, Lucas; Dorival, Céline; Carrat, Fabrice; Pol, Stanislas; Fontaine, Hélène; Sarica, Nazim; Neuveut, Christine; Housset, Chantal; Kremdsorf, Dina; Schnuriger, Aurélie; Soussan, Patrick |
| Contributors: |
Centre de Recherche Saint-Antoine (CRSA); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); CHU Henri Mondor Créteil; Groupe Henri Mondor-Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Matière et Systèmes Complexes (MSC); Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); CHU Saint-Antoine AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Département d'hépatologie CHU Cochin; Hôpital Cochin AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut de génétique humaine (IGH); Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); CHU Trousseau APHP; CHU Tenon AP-HP; ANR-19-COHO-0002,Hepather (COHORTES),Therapeutic options for hepatitis B and/or C: a French nationwide cohort study(2019) |
| Source: |
ISSN: 1936-0533. |
| Publisher Information: |
CCSD; Springer Internat. Publ |
| Publication Year: |
2022 |
| Subject Terms: |
Alternative splicing; Chronic hepatitis; Chronic infection; HBV; HBV pregenomic RNA; Liver disease; Viral circulating forms; Viral cycle; Viral genome diversity; Viral hepatitis; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Background: Besides the prototypical hepatitis B virus (HBV) infectious particle, which contains a full-length double-stranded DNA (flDNA), additional circulating virus-like particles, which carry pregenomic RNA (pgRNA), spliced1RNA (sp1RNA) or spliced-derived DNA (defDNA) forms have been described. We aimed to determine the level of these four circulating forms in patients and to evaluate their impact on viral lifecycle.Methods: Chronic HBV untreated patients (n = 162), included in the HEPATHER cohort, were investigated. Pangenomic qPCRs were set up to quantify the four circulating forms of HBV nucleic acids (HBVnaf). In vitro infection assays were performed to address the impact of HBVnaf.Results: Hierarchical clustering individualized two clusters of HBVnaf diversity among patients: (1) cluster 1 (C1) showing a predominance of flDNA; (2) cluster 2 (C2) showing various proportions of the different forms. HBeAg-positive chronic hepatitis phase and higher viral load (7.0 ± 6.4 vs 6.6 ± 6.2 Log10 copies/ml; p < 0.001) characterized C2 compared to C1 patients. Among the different HBVnaf, pgRNA was more prevalent in C1 patients with high vs low HBV viral load (22.1% ± 2.5% vs 4.1% ± 1.8% of HBVnaf, p < 0.0001) but remained highly prevalent in C2 patients, whatever the level of replication. C2 patients samples used in infection assays showed that: (1) HBVnaf secretion was independent of the viral strain; (2) the viral cycle efficiency differed according to the proportion of HBVnaf in the inoculum, independently of cccDNA formation. Inoculum enrichment before infection suggests that pgRNA-containing particles drive this impact on viral replication.Conclusion: Besides the critical role of HBV replication in circulating HBVnaf diversity, our data highlight an impact of this diversity on the dynamics of viral cycle.Clinical trial registration: Patients were included from a prospective multicenter French national cohort (ANRS CO22 HEPATHER, NCT01953458). |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35927368; PUBMED: 35927368 |
| DOI: |
10.1007/s12072-022-10389-6 |
| Availability: |
https://hal.sorbonne-universite.fr/hal-03843715; https://hal.sorbonne-universite.fr/hal-03843715v1/document; https://hal.sorbonne-universite.fr/hal-03843715v1/file/hal-03843715.pdf; https://doi.org/10.1007/s12072-022-10389-6 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.68BAACC0 |
| Database: |
BASE |