The Family contains 6 genera divided between 2 subfamilies:
| Genus: | Type species: | Host organism: | Parvovirinae: |
|---|---|---|
| Parvovirus | Mice minute virus | Vertebrates |
| Erythrovirus | B19 virus | Vertebrates |
| Dependovirus | Adeno-associated virus 2 | Vertebrates | Densovirinae: |
| Densovirus | Junonia coenia densovirus | Invertebrates |
| Iteravirus | Bombyx mori densovirus | Invertebrates |
| Contravirus | Aedes aegypti densovirus | Invertebrates |
The Dependoviruses were the first to be discovered. Unlike the other 5 genera, these are replication-defective viruses which are entirely dependent helper viruses. The genus consists of 4 types of adeno-associated viruses (AAV1-4) which require Adenoviruses (or Herpesviruses) for helper functions to replicate. The adenovirus genes involved are early (regulatory) rather than late (structural), such as E1A, but it has recently been shown that treatment of cells with U.V, cycloheximide or some carcinogens can replace the requirement for helper virus. Therefore the requirement appears to be for a modification of the cellular environment rather than a specific virus protein - probably affecting transcription of the defective virus genome.
Morphology:
Particles are icosahedral, 18-26nm diameter & consist only of protein (50%) + DNA (50%).
There are 3 capsid proteins, VP1-3. VP3 is derived by protease cleavage of VP2. Infectious virions of canine parvovirus contain 60 protein subunits that are predominantly VP-2. The central structural motif of VP-2 has the same topology (an eight-stranded antiparallel beta-barrel) as has been found in many other icosahedral viruses (e.g. picornaviruses).
The capsid confers considerable stability on the virions, which are resistant to inactivation by pH, solvents or high temperatures (1h @ 50°C).
To view a negatively stained electron micrograph of AAV, click here. In this image, the larger adenovirus particles (diameter 60-90nm) are easily distinguishable from the smaller Dependovirus particles (diameter ca. 20nm).
To view a computer-generated image of canine parvovirus reconstructed from crystallographic data, click here.
Genome:
Linear, non-segmented, s/s DNA, ~5kb. Most of the strands packaged seem to be (-)sense, but AAVs package equal amounts of (+) and (-) strands, and all seem to package at least a proportion of (+)sense strands. The ends of the genome have palindromic sequences of ~115nt which form "hairpins". These structures are essential for the initiation of genome replication.
Replication:
The pathogenic human parvovirus B19 is difficult to grow in culture, so comparatively little is known about its biology. The receptor molecule for B19 is tetrahexosoceramide, a glycolipid (erythrocyte P antigen) - explains cell tropism of B19:
Expression of the Parvovirus genome is poorly understood. The helper function required by the defective viruses is thought to be involved in transcription of virus genes. Host cell DNA polymerase is necesary for genome replication.
In the absence of helper virus, Dependoviruses can establish a latent infection; in this state, the virus genome is integrated into the host cell DNA - & can be rescued >50 passages later by Adenovirus infection. The rep gene is involved in this process, which is poorly understood. There is evidence for vertical transmission of avian AAV in chickens. Conversely, AAV appears to inhibit cellular transformation by Adenoviruses.
Pathogenesis:
Parvoviruses cause infections in a wide variety of birds and mammals, but 70-90% of most human populations are seropositive. The pathology of Parvoviruses is shaped by their dependence on cellular functions for replication - cell tropism is broad, but since cells must pass through S-phase, they tend to infect rapidly dividing tissues, most commonly:
This involves an acute depression in the production of red blood cells from the bone marrow, directly due to infection of reticulocytes. This is a transient event which is usually not of great clinical significance except in patients with other haematological diseases, e.g. sickle-cell disease. This is followed by a rubella-like rash, usually the most obvious symptom of B19 infection. Children are much more likely than adults to develop the rash (not all do), which is known as erythaema infectiosum (EI), "fifth disease" or "slapped cheek disease".
In ~80% patients, there is also arthropathy - temporary arthritis-like joint involvement (particularly in adults).
B19 infection in pregnancy is also associated with early foetal loss, although the probability of this appears to be low (<10%).
Treatment/Prevention: None, although immune globulin has been used in chronic parvovirus infection of immunocompromised patients.
