Molecular Organization Of Parvoviruses

The genome of parvoviruses consist of approx a 5-kilobase (kb) linear, monopartite, single-stranded DNA (3-5). At both the ends of the genome are sequences known as terminal palindromes, which do not encode any protein. The parvoviral genome consists of only two overlapping genes that encode two types of proteins. The genetic map of parvoviruses can be broadly divided into left- and right-halves that encode regulatory and capsid proteins respectively. The regulatory protein involved in replication is known as Rep or NS (for nonstructural protein) and the structural capsid protein is referred to as VP. There are two major promoters in the viral genome that express the rep/NS and VP proteins. In addition, AAV genome also contains a third promoter, which transcribes smaller rep proteins. By alternate splicing, the proteins are generated in different molecular sizes. Nonetheless, the isotypes of rep/NS and VP share same C-terminal amino acid sequences. A fully assembled parvovirus capsid forms an icosa-hedral structure of approx 20 to 25 nm. Electron micrographs have shown icosahedral particles made up of multiple capsomeres, which are easily distinguished from those of most other virus groups by their smaller size. Recent studies on AAV capsids have indicated that in a fully assembled capsid, about 60 individual protein molecules are present (6). A prototypic parvoviral structure and genome is shown in Fig. 1.

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