Properties of Parvoviridae

Only 20-25 nm in diameter, the Parvoviridae (Table 17-1) consist of a simple icosahedral shell surrounding a linear single-stranded DNA molecule of very limited coding potential (5 kb for human parvovirus B19 and 4.7 kb for human dependoviruses). The three-dimensional atomic structure of canine parvovirus has been solved by X-ray crystallography, revealing a capsid composed of one major and two minor polypeptides arranged to form 60 protein subunits. The virus is very stable, resisting 60°C for some hours and variation from pH 3 to 9.

The ssDNA parvovirus genome is of negative polarity, but some virions (up to 50% of them in the case of the genus Dejiendovirua) package a positive

Table 17-1

Properties of Pimxmntlae

Three mammalian genera PflitwiiHS, Eri/ihwirr/^, and Dr/riiiiwints

Icosahedral virion, 20-25 nm, capsid composed of 60 prolein subunits l.incar minus sense ssDNA genome, 5 kb, palindromic hairpins at each end

Unique mechanism of DMA replication

Replicate in nucleus of cycling cells, using cellular enzymes

Relatively stable to heat (60*0 and pH (3-9)

OrpcHtiovirus usually requires helper virus; persists by integration strand instead. The genomes of several human and animal parvoviruses have been sequenced, and all display long terminal palindromic sequences enabling each end of the molecule to fold back on itself to form a hairpin structure

There are two genera of parvoviruses that contain viruses of humans. The genus Dcpcndovirus was so named because the only known representatives, the human "adeno-associated viruses" (AAV), are usually found in association with an adenovirus which serves as a helper in their replication (Fig. 17-1 A). The dependoviruses were, therefore, assumed to be defective and to be absolutely dependent on a helper adenovirus (or herpesvirus) for their replication, but this is now recognized to be not entirely true (see below). The genus Parvovirus (Fig. 17-1B) contains several viruses of animals and some that may cause diarrhea in humans; parvovirus B19 has now been allocated to a separate genus, Erythrovirus.

Viral Replication

Unlike those double-stranded DNA viruses (e.g., polyomavirus) that induce resting host cells to enter the S phase, the tiny ssDNA parvoviruses lack this capacity and hence can replicate only in dividing cells Parvoviruses replicate in the nucleus; transcription and replication of the genome occur there, the nonstructural proteins accumulate there, and virions assemble there. There are no enzymes in the virion itself; a cellular DNA polymerase is used to transcribe the viral ssDNA into dsDNA, which then serves as the template for transcription of mRNA by cellular DNA-dependent RNA polymerase II. Nonstructural proteins are encoded by the left side of the genome and structural proteins by the right. Alternative splicing patterns give rise to several mRNA species which are translated into a greater number of different proteins than the limited coding potential of the short genome might suggest. The splicing program differs from one parvovirus to another. Certain nonstructural proteins serve to /ransactivate the viral promoter(s) and to down-regulate transcription from certain cellular promoters.

The mechanism of replication of the genome is extraordinary. The palindromic 3'-terminal sequence serves as a self-primer for initiation of synthesis of a plus sense DNA strand to give a double-stranded replica five intermediate from which progeny minus strands are in turn transcribed, again using the hairpin structure as a primer. The detection in infected bone marrow cells of a dimeric form of the replicative intermediate, in which each of

Properties of Parvoviridae

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