Overview of Parvovirus DNA Replication

Parvoviruses are small viruses with single-stranded, linear DNA genomes. These viruses are non-enveloped and contain a small genome (4-6 kb) that is encapsulated in a protein capsid. The family Parvoviridae includes viruses that replicate in the nuclei of both invertebrate and vertebrate hosts. Examples include the Minute Virus of Mice (MVM) and Adeno-Associated Viruses (AAV), which require co-infection with helper viruses for replication.


Both MVM and AAV use a single-stranded DNA genome to encode their proteins. The genome is divided into two main sections: one that codes for capsid proteins and another for nonstructural proteins (Rep or NS proteins) needed for DNA replication. These viruses efficiently use their genome with overlapping reading frames and regulatory elements for transcription and splicing.


Rolling-Hairpin Replication Mechanism

The DNA replication of parvoviruses follows a mechanism similar to "rolling-circle" replication seen in prokaryotes. Upon infection, the viral single-stranded DNA is converted into a duplex intermediate. The terminal sequences of the DNA genome are palindromic and form hairpins, which allow the host polymerase to synthesize the complementary strand. This process generates a duplex intermediate, with the viral 3’ telomere covalently linked at one end.


In some parvoviruses, such as AAV2, this structure initiates replication by activating the Rep protein. However, in others like MVM, it does not act as a replication origin. The major amplification of the viral genome occurs through concatemeric duplex intermediates, using a unidirectional, single-strand-specific replication mechanism.