Influence of Protein-Protein Interactions (PPIs) on the outcome of viral infections

As genetic parasites, viruses exploit the hosts molecular machinery to fulfill their life cycle. This is largely determined by Protein-Protein Interactions (PPIs) that mediate critical steps in virus replication (e.g., attachment, entry, replication and virion assembly) and virus clearance (e.g., antibody- and cell-mediated immune responses). Their importance has been neatly reflected in the ongoing SARS-CoV-2 pandemic as newly appearing spike variants are being extensively studied to assess their impact on the interaction with their cognate receptor (human ACE2) and their evasion of the antiviral immune responses such as neutralizing antibodies. Viruses exploit many of their proteins to establish a catalog of virus-host PPIs, where each PPI has the potential to act as a rheostat of infection. Therefore, it is critical to characterize the complete set of virus-host PPIs underpinning viral infection and elucidate how they are influenced by amino acid sequence variation.

Uncovering the complete set of virus-host PPIs and how amino acid variants can finely tune this network is a challenging task. It requires a cross-talk between computational and experimental approaches, bringing together protein structure and functional data into a single PPI network to: i) identify virus-host protein interfaces of pharmacological interest; ii) rapidly assess zoonotic potential of (re)emerging viruses as well as novel virus strains and; iii) better understand the genetic determinants of virus entry, replication and disease. This Research Topic focuses on computational and experimental efforts to decipher virus-host PPIs and how amino acid sequence variation influence viral infection. In particular, we encourage manuscripts that integrate computational and experimental methods.

This Research Topic will accept Original Research, Reviews, Perspective and Opinion articles focusing on:
• Prediction of virus-host PPIs
• Experimental elucidation and/or characterization of virus-host PPIs
• Structural biology of virus-host protein complexes
• Amino acid sequence variation in virus and host proteins influencing viral infection, including host range, virus entry, replication, assembly and pathogenesis
• Computational and experimental approaches to design mutations that strengthen or weaken virus-host PPIs
• Antibody recognition and neutralization-escape mutants
• Mechanisms of antibody-mediated protection