Bouslama, Z. | Search bioRxiv

bioRxiv2024

Tracing the evolutionary history of Tunisian HPV 16 and 18 across the genetic diversity in L1 gene

HPV16 and HPV18 are the most prevalent high risk HPV types, recognized to be HPV vaccine target. Currently, available vaccines against HPV infections are based on virus-like particles (VLPs) derived from the L1 protein. Understanding the emergence of HPV isolates and exploring the genetic diversity of their L1 gene is crucial to assess the effectiveness of vaccine introduction in different populations. This is the first study aiming to investigate the evolutionary dynamics of HPV16 and HPV18 variants circulating in Tunisia. We constructed evolutionary history of HPV16 and HPV18 based on partial L1 sequence dataset of 733 Tunisian and worldwide representative isolates. Phylogeographic analysis confirmed the European origin of Tunisian strains that have emerged in 90s. Strikingly, four nonsense mutations in HPV16 and one in HPV18 within the HI surface loop, a critical immunogenic region were identified. Moreover, the latter showed an excess of non-synonymous over synonymous substitutions, a hallmark of local adaptation. By elucidating the genetic variability in the L1 gene, our study unveils several new features that pose challenges to the ongoing fight against HPV. These insights underscore the importance of continuous surveillance and adaptation of vaccination strategies to address evolving viral dynamics effectively. ImportanceHuman Papillomavirus (HPV) is a virus known to cause cervical cancer (CC). HPV16 and HPV18 are the most common HPV types related to CC. This study aimed to trace the evolutionary history of Tunisian HPV16 and HPV18 isolates. Phylogeographic analysis showed that these viruses were originated from Europe and emerged in 1990s. Several genetic changes have been identified in the L1 gene of HPV16 & 18 that could potentially reduce the effectiveness of HPV vaccines. By understanding these changes and addressing the local adaptation of HPVs, we could prevent the spread of this virus within a population.

evolutionary biology↗

bioRxiv2020

In silico study of the spike protein from SARS-CoV-2 interaction with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism

The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.

bioinformatics↗