The evolutionary process of genetic recombination has the potential to rapidly change the properties of a viral pathogen, and its presence is a crucial factor to consider in the development of treatments and vaccines. It can also significantly affect the results of phylogenetic analyses and the inference of evolutionary rates. The detection of recombination from samples of sequencing data is a very challenging problem and is further complicated for SARS-CoV-2 by its relatively slow accumulation of genetic diversity. The extent to which recombination is ongoing for SARS-CoV-2 is not yet resolved. To address this, we use a parsimony-based method to reconstruct possible genealogical histories for samples of SARS-CoV-2 sequences, which enables us to pinpoint specific recombination events that could have generated the data. We propose a statistical framework for disentangling the effects of recurrent mutation from recombination in the history of a sample, and hence provide a way of estimating the probability that ongoing recombination is present. We apply this to samples of sequencing data collected in England and South Africa and find evidence of ongoing recombination.
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http://dx.doi.org/10.1093/molbev/msac028 | DOI Listing |
Viruses
December 2024
Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225012, China.
The ongoing global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the continuous development of innovative vaccine strategies, especially in light of emerging viral variants that could undermine the effectiveness of existing vaccines. In this study, we developed a recombinant virus-like particle (VLP) vaccine based on the Newcastle Disease Virus (NDV) platform, displaying a stabilized prefusion form of the SARS-CoV-2 spike (S) protein. This engineered S protein includes two proline substitutions (K986P, V987P) and a mutation at the cleavage site (RRAR to QQAQ), aimed at enhancing both its stability and immunogenicity.
View Article and Find Full Text PDFSci Rep
January 2025
Division of Metabolic Disorders, CHOC Children's Hospital, Orange, CA, 92868, USA.
Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease.
View Article and Find Full Text PDFCardiovasc Ther
January 2025
Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei Province, China.
Acute coronary syndrome (ACS) is one of the most common leading global causes of mortality, encompassing ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). Percutaneous coronary intervention (PCI) has become a pivotal therapeutic approach for ACS, underscoring the importance of anticoagulation strategies. Among the commonly employed anticoagulants in PCI, heparin and bivalirudin take precedence, with heparin serving as the archetypal choice.
View Article and Find Full Text PDFBackground: In TALAPRO-2, the poly(ADP-ribose) polymerase inhibitor talazoparib plus the androgen receptor-signaling inhibitor enzalutamide improved radiographic progression-free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51-0.
View Article and Find Full Text PDFIntroduction: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.
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