Background: Viral quasispecies dynamics between pre- and post-nucleos(t)ide analog (NA) therapy remains unclear.
Aim: This study aimed to investigate the HBV quasispecies evolution and its relationship with durability of off-therapy responses in HBeAg-negative chronic hepatitis B (CHB) patients who stopped NA therapy.
Methods: Fifty-four HBeAg-negative CHB patients who stopped NAs, including 19 virological controllers (VC) who maintained serum HBV DNA < 2000 IU/mL beyond 1-year off-therapy, and 35 virological relapsers (VR) experiencing virological relapse within 1-year off-therapy were recruited. Viral quasispecies was analyzed by deep sequencing. Hepatitis B core-related antigen (HBcrAg) and HBsAg were also measured.
Results: VC had significantly higher baseline viral quasispecies diversity of the precore/core gene, measured by nucleotide diversity, than VR. Low baseline viral nucleotide diversity (< 0.01) and high HBcrAg (≧ 2.0 KU/mL), but not HBsAg, at end of treatment (EOT) were significantly associated with higher risk of 1-year virological relapse (hazard ratio [HR] 6.09 and 3.31, respectively). Combination of low baseline viral nucleotide diversity and high HBcrAg at EOT could identify patients at high risk (HR 15.82). Further analysis of the evolution of HBV whole genome showed that HBV nucleotide diversity negatively correlated with serum HBV DNA levels. Notably, the viral quasispecies diversity between pre- and post-NA treatment remained relatively unchanged.
Conclusion: Higher baseline HBV quasispecies diversity associates with more durable off-therapy viral suppression in HBeAg-negative CHB patients. Combination of baseline viral nucleotide diversity and HBcrAg at EOT can identify patients at high risk for virological relapse after stopping NAs.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/s12072-021-10186-7 | DOI Listing |
PLoS Pathog
January 2025
Institute of Medical Virology, University of Zurich (UZH), Zurich, Switzerland.
For use in prevention and treatment, HIV-1 broadly neutralizing antibodies (bnAbs) have to overcome Env conformational heterogeneity of viral quasispecies and neutralize with constant high potency. Comparative analysis of neutralization data from the CATNAP database revealed a nuanced relationship between bnAb activity and Env conformational flexibility, with substantial epitope-specific variation of bnAb potency ranging from increased to decreased activity against open, neutralization-sensitive Env. To systematically investigate the impact of variability in Env conformation on bnAb potency we screened 126 JR-CSF point mutants for generalized neutralization sensitivity to weakly neutralizing antibodies (weak-nAbs) depending on trimer opening and plasma from people with chronic HIV-1 infection.
View Article and Find Full Text PDFNat Commun
December 2024
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.
Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we here deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of the Spike gene in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets.
View Article and Find Full Text PDFVirus Res
January 2025
Department of Virology, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro (PD), Italy.
Among flaviviruses, Zika virus (ZIKV) is the only arbovirus officially recognized as a teratogenic agent, as a consequence of its ability to infect and cross the placental barrier causing congenital malformation in the fetus. While many studies have focused on understanding ZIKV pathogenesis during pregnancy, the viral mechanisms affecting fetal development remain largely unclear. In this study, we investigated ZIKV virulence in placental trophoblasts, using viruses with distinct lipid profiles.
View Article and Find Full Text PDFVirology
December 2024
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Avenida Rivadavia 1917, C1083ACA Ciudad Autónoma de Buenos Aires, Argentina; Laboratorio de Virología y Genética Molecular (LVGM), Facultad de Ciencias Naturales y Ciencias de la Salud, Universidad Nacional de la Patagonia San Juan Bosco, Belgrano 160, Trelew, CP, 9100, Argentina. Electronic address:
Intra-host viral variability is related to pathogenicity, persistence, drug resistance, and the emergence of new clades. This work reviews the large amount of data on SARS-CoV-2 intra-host variability accumulated to date, addressing known and potential implications in COVID-19 and the emergence of VOCs and lineage-defining mutations. Topics covered include the distribution of intra-host polymorphisms across the genome, the corresponding mutational signatures, their patterns of emergence and extinction throughout infection, and the processes governing their abundance, frequency, and type (synonymous, nonsynonymous, indels, nonsense).
View Article and Find Full Text PDFVirol J
December 2024
Department of Molecular and Translational Medicine, Section of Microbiology, University of Brescia, Piazzale Spedali Civili, 1, Brescia, 25123, Italy.
Background: Since the beginning of the pandemic, contact tracing has been one of the most relevant issues to understand SARS-CoV-2 transmission dynamics and, in this context, the analysis of quasispecies may turn out to be a useful tool for outbreak investigations. Analysis of the intra-host single nucleotide variants (iSNVs) found in the nsp2, ORF3, and ORF7 genes of SARS-CoV-2 was conducted in order to correctly identify virus transmission chain among patients hospitalized in Brescia Civic Hospital.
Methods: During the period between August and October 2023, 13 nasopharyngeal specimens, collected from patients admitted to Brescia Civic Hospital, were tested for SARS-CoV-2 positivity and molecularly characterized.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!