Speaker
Description
The early 21st century has witnessed the emergence of two coronaviral epidemics, SARS-CoV-1 (2003), MERS-CoV (2012), and a global pandemic caused by SARS-CoV-2 (2019). Despite the notable efficacy of vaccines, their imperfections, including waning immunity and emerging antigenic variants, underscore the need for continuous research in viral evolution and antigenic drift. Recognizing the potential threat posed by the Coronaviridae family and the uncertainty surrounding the origin of the next pandemic-causing pathogen, this study emphasizes the importance of investing in applied research focused on understanding the viral evolution of microbial families with pandemic potential, prototype, and related organisms.
The study centers on HCoV OC43, a model organism with a rich evolutionary history spanning over six decades. Its propensity for reinfection and close relation to SARS-CoV-2 make it an ideal candidate for studying Coronavirus evolution.
Herein, we sequenced OC43 samples collected over an eight-year period (2010-2018) from a geographically restricted region. The study aims to track population level interhost diversity of OC43 in a prospective cohort from a specific region over time using consensus based approach. High throughput single genome PacBio sequencing was used to delineate intra-host diversity of HCoV-OC43 genome sequences within individuals in this cohort, with a focus on hemagglutinin esterase (HE) and spike (S) genes. PacBio SMRT sequencing is utilized to preserve haplotype-level information, a critical aspect often overlooked in conventional consensus-based sequencing approaches. To achieve this, RNA extracted from OC43 positive nasal swabs underwent reverse transcription, incorporating a 12-nucleotide unique molecular identifier. Subsequently, PCR amplification and PacBio SMRT sequencing of a ~5.7 Kb region encompassing S and HE genes were performed. The output provides hundreds of single-copy sequences per sample, enhancing our capacity to discern low-frequency haplotypes with precision and sensitivity.
The findings of this study revealed immune-based positive selection and recombination (fubar and SimPlot analysis among other computational analyses) as prominent modes of evolution for OC43 in this cohort. Extrapolating these findings to the context of SARS-CoV-2 suggests that vaccines may necessitate periodic 'upgrades' to effectively address the ever-evolving viral strains. Moreover, the prospect of SARS-CoV-2 persisting and causing seasonal outbreaks adds a layer of complexity to our understandings. The findings emphasize the imperative for continuous research endeavors and strategic preparedness initiatives, essential for navigating the intricate terrain of viral evolution. Such proactive measures are pivotal in fortifying our capabilities to combat 'Pathogen X’.
