Conformational Dynamics of Nonenveloped Circovirus Capsid to the Host Cell Receptor

Abstract

Summary Circovirus, comprising one capsid protein, is the smallest nonenveloped virus and induces lymphopenia. Circovirus can be used to explore the cell adhesion mechanism of nonenveloped viruses. We developed a single-molecule fluorescence resonance energy transfer (smFRET) assay to directly visualize the capsid's conformational feature. The capsid underwent reversible dynamic transformation between three conformations. The cell surface receptor heparan sulfate (HS) altered the dynamic equilibrium of the capsid to the high-FRET state, revealing the HS-binding region. Neutralizing antibodies restricted capsid transition to a low-FRET state, masking the HS-binding domain. The lack of positively charged amino acids in the HS-binding site reduced cell surface affinity and attenuated virus infectivity via conformational changes. These intrinsic characteristics of the capsid suggested that conformational dynamics is critical for the structural changes occurring upon cell surface receptor binding, supporting a dynamics-based mechanism of receptor binding.

Molecular basis for the different PCV2 susceptibility of T-lymphoblasts in Landrace and Piétrain pigs

“…PCV2 is a non-enveloped virus that does not disassemble by fusing with the endosomal membrane. During infection, viral particles experience conformational changes to respond to various external stimuli [ 55 – 57 ], such as binding to cell receptors [ 58 , 59 ], proteolysis [ 60 , 61 ], changes in bivalent cation concentrations [ 62 , 63 ], or endosomal acidification [ 60 , 64 , 65 ]. Moreover, membrane-modifying proteins physically penetrate the endosomal membrane [ 53 ], causing endosome membrane distortion and disruption.…”