MicrobiologyBytes: Virology: Parvoviruses Updated: August 18, 2010 Search

Parvoviruses

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Introduction:

Parvoviruses are among the smallest, simplest eukaryotic viruses and were only discovered in the 1960's. They are widespread in nature; human Parvovirus infections were only recognised in the 1980's. Essentially, they fall into two groups, defective viruses which are dependent on helper virus for replication and autonomous, replication-competent viruses. In all, >50 parvoviruses have been identified.

The family contains six genera divided between two subfamilies:

Family

(Subfamily)

Genus

Type Species

Hosts

Parvoviridae:

 

 

Parvovirinae
Parvovirus Mice minute virus Vertebrates
Erythrovirus B19 virus Vertebrates
Dependovirus Adeno-associated virus 2 Vertebrates
Amdovirus Aleutian mink disease virus Vertebrates
Bocavirus Bovine parvovirus Vertebrates
Densovirinae
Densovirus Junonia coenia densovirus Invertebrates
Iteravirus Bombyx mori densovirus Invertebrates
Brevidensovirus Aedes aegypti densovirus Invertebrates
Pefudensovirus Periplanta fuliginosa 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:

Parvovirus particles are icosahedral, 18-26nm diameter & consist only of protein (50%) + DNA (50%). There are three 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). Kaufmann B, et al. (2004) The structure of human parvovirus B19. PNAS USA 101: 11628-116336.

The capsid confers considerable stability on the virions, which are resistant to inactivation by pH, solvents or high temperatures (1h @ 50°C).

Negatively stained electron micrograph of AAV. In this image, the larger adenovirus particles (diameter 60-90nm) are easily distinguishable from the smaller Dependovirus particles (diameter ca. 20nm). Computer-generated image of canine parvovirus reconstructed from crystallographic data.

Genome:

Linear, non-segmented, s/s DNA, ~5kb. Parvovirus genomes are (-)sense, but the replication-defective AAVs package equal amounts of (+) and (-) strands into virions. The ends of the genome have palindromic sequences of ~115nt which form "hairpins". These structures are essential for the initiation of genome replication, and also control which strand(s) is packaged.

Parvovirus hairpins

 

Replication:

The pathogenic human parvovirus B19 is difficult to grow in culture, so comparatively little is known about its biology. Globotetraosylceramide (Gb4Cer), a glycosphingolipid (erythrocyte P antigen), forms part of the receptor molecule for B19 - this explains cell tropism of B19:
Parvovirus replication
How Do Animal DNA Viruses Get To The Nucleus? Ann.Rev.Microbiol. (1998) 52: 627-686

Replication occurs in the nucleus & is thought to follow the scheme above. All Parvoviruses are highly dependent on cellular functions for genome replication. The autonomous viruses require the cell to pass through S-phase for replication to occur, but unlike Polyomaviruses (below) cannot turn on host cell DNA synthesis. The defective viruses are even more dependent - require host cell machinery plus helper virus for replication.

Parvovirus gene expression

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:

The best known human Parvovirus is referred to as B19. First discovered in 1974, it was only in 1981 that its association with aplastic crisis in children was first realized.

 

B19 infection

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%).

Recent reports suggest that AAV infection in human semen may contribute to male infertility, although the evidence for this is still tentative.

Treatment/Prevention: None, although immune globulin has been used in chronic parvovirus infection of immunocompromised patients.

Recent molecular studies appear to suggest that there may be a second human parvovirus, for which the name human Bocavirus (HBoV) has been proposed: Allander T. et al 2005 Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci USA.

Feline Parvovirus and Canine Parvovirus are serious veterinary pathogens. Vaccines against both now exist and are widely used.
Aleutian disease virus (named after strain of mink in which it is most frequently seen) infects mink, causing persistent infections. Control is usually by slaughter.

 

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Gene Therapy:

AAV have recieved considerable attention in recent years as vectors for gene therapy: but:

Tal J. (2000) Adeno-associated virus-based vectors in gene therapy. J Biomed Sci. 7: 279-291.

 

Human Bocavirus

Human Bocavirus (HBoV) was identified as a human pathogen in September 2005 (Allander T, et al. Cloning of a human parvovirus by molecular screening of respiratory tract samples. PNAS USA 2005 102: 12891–6). HBoV has been since found in children with respiratory tract illnesses in practically all areas of the world in which it has been investigated, an indication of its wide dissemination, and recent data indicate that it may also be associated with gastroenteritis and excreted in faeces (Vicente D, et al. Human bocavirus, a respiratory and enteric virus. Emerg Infect Dis April 2007). Further investigations to confirm the association between HBoV and human illness are required.


Brown, K.E. and Young, N.S. (1997) Parvovirus B19 in Human Disease. Ann.Rev.Med. 48: 59-67

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