Biology

Dr. Manidipa Banerjee
IIT, Delhi

Non-enveloped viruses employ small hydrophobic or amphipathic peptides to breach the host membrane barrier during cellular entry. The nature of capsid conformational changes required for the exposure of these peptides, and subsequent release of viral genome, as well as the molecular mechanism of host membrane penetration, remains unclear for most viruses. We are utilizing two non-enveloped RNA viruses, a mammalian virus – Hepatitis A Virus (HAV), and an insect virus – Flock House Virus (FHV), in order to understand capsid structural dynamics during cellular entry and membrane penetration. We have identified a small peptide VP4, a structural component of HAV capsid, as the potential host membrane-disrupting agent during cellular entry. Using a combination of biophysical assays and molecular dynamics simulation studies, we have shown that VP4 likely forms small pores in the endosomal membranes, allowing the release of HAV genome in the cytosol. Analogous studies carried out with the membrane-penetrating peptide of FHV, designated gamma, has indicated that the process of host membrane disruption by different non-enveloped viruses is likely to be mechanistically diverse. TEM and cryo-EM based studies on FHV variants has provided some indication of structural constraints and alterations required for membrane interaction and capsid disassembly.