Dependoparvoviruses

Dependoparvoviruses are a genus within the Parvoviridae family of small, nonenveloped, icosahedral viruses with a linear single-stranded DNA genome. They are defined by their requirement for a helper virus to replicate, most commonly an adenovirus or a herpesvirus. The best known member is the adeno-associated virus (AAV), which includes multiple serotypes with differing tissue preferences.

The genome is about 4.7 kilobases in length and contains two main coding regions: rep, which encodes replication and genome processing proteins, and cap, which encodes the structural capsid proteins VP1, VP2, and VP3. Flanking the genome are inverted terminal repeats that function as origins of replication and packaging signals. Rep proteins regulate replication and site-specific processes, while Cap proteins form the virion capsid. In the absence of a helper virus, replication is markedly reduced; in some cases the genome can persist as an episome, and AAV2 is known to integrate at a preferred site on chromosome 19 (AAVS1) at low frequency.

Biology and host range: dependoparvoviruses can infect a broad range of vertebrate hosts, with serotype-specific tissue tropism. They are typically nonpathogenic in humans, and infections are often asymptomatic unless a helper virus is present or integration events disrupt host genes. The dependence on helper functions distinguishes them from autonomous parvoviruses.

Applications and significance: recombinant AAV (rAAV) vectors are widely used in gene therapy due to low pathogenicity, broad tissue tropism, and the ability to achieve long-term expression in non-dividing cells. rAAV vectors carry a transgene flanked by ITRs and have a packaging capacity of roughly 4.7 kb. Several serotypes enable targeted delivery, and licensed therapies (for example, retinal and muscular dystrophy indications) illustrate the clinical impact of dependoparvoviruses.