Structures and functions of parvovirus capsids and the process of cell infection.
To infect a cell, the parvovirus or adeno-associated virus (AAV) genome must be delivered from outside the plasma membrane to the nucleus, and in the process, the capsid must follow a series of binding and trafficking steps and also undergo necessary changes that result in exposure or release the ssDNA genome at the appropriate time and place within the cell. The 25 nm parvovirus capsid is comprised of two or three forms of a single protein, and although it is robust and stable, it is still sufficiently flexible to allow the exposure of several internal components at appropriate times during cell infection. The capsid can also accommodate insertion of peptides into surface loops, and capsid proteins from different viral serotypes can be shuffled to create novel functional variants. The capsids of the different viruses bind to one or more cell receptors, and for at least some viruses, the insertion of additional or alternative receptor binding sequences or structures into the capsid can expand or redirect its tropism. The infection process after cell binding involves receptor-mediated endocytosis followed by viral trafficking through the endosomal systems. That endosomal trafficking may be complex and prolonged for hours or be relatively brief. Generally only a small proportion of the particles taken up enter the cytoplasm after altering the endosomal membrane through the activity of a VP1-encoded phospholipase A2 domain that becomes released to the outside of the viral particle. Modifications to the capsid that can occur within the endosome or cytoplasm include structural changes to expose internal components, ubiquination and proteosomal processing, and possible trafficking of particles on molecular motors. It is still not clear how the genomes enter the nucleus, but nuclear pore-dependent entry of particles or permeabilization of nuclear membranes have been proposed. Those processes control the infection, pathogenesis, and host ranges of the autonomous viruses and determine the effectiveness of gene therapy using AAV capsids.
Parrish
Colin R
CR
Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. crp3@cornell.edu
D000818:Animals; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry* / Q000502:physiology*; D011992:Endosomes / Q000821:virology; D006801:Humans; D017992:Parvovirus / Q000502:physiology*; D019065:Virus Assembly; D053586:Virus Internalization