Pseudo-Infection Model: A Bottom-Up Synthetic Approach to Cellular Entry of Enveloped Viruses and Virus Mimics

Viruses are the most abundant biological entities on Earth. They function as obligate intracellular parasites across all three domains of life. Enveloped viruses, which are surrounded by a lipid membrane, are known to cause significant pandemics and epidemics. Understanding their molecular functions and life cycle is crucial, but studying them in native conditions can be challenging. The pseudo-infection model of viral cellular entry is a bottom-up synthetic approach that focuses on enveloped virus binding and fusion with suitably designed target membranes in a minimal cell-free fashion. This experimental model recapitulates the steps of viral attachment and plasma membrane/endosomal membrane fusion using membrane architecture such as lipid vesicles, and supported lipid bilayers of well-defined compositions, or cell-derived membranes. So far, this model has been highly useful for understanding the molecular determinants and kinetics of viral cellular entry. The pseudo-infection model also provides a novel platform for designing and assessing antiviral strategies. Here, recent developments involving membrane fusion of enveloped viruses or virus-mimetic systems are brought together under the umbrella term pseudo-infection model to highlight the underlying commonalities. In addition, the recent conceptual and technical advancements are outlined in understanding viral fusion and related applications.