On infection of a nonpermissive cell (one that has not
dogs and myocarditis in pups, which often leads to death from
been infected by a helper and is otherwise nonpermissive),
acute heart failure. It was called CPV-2 to distinguish it from
AAV establishes a latent infection in which its DNA inte-
a previously known canine parvovirus called minute virus of
grates into the host chromosome. In human cells integration
canines, which is sometimes referred to as CPV-1. CPV-2 is
is specific--it occurs on chromosome 19 within a defined
closely related to FPV and to parvoviruses that circulate in
region. There appears to be a binding site for the nonstruc-
foxes and other wild animals, all of which share 98% sequence
tural protein at this location that directs integration to a site
identity. Molecular genetic studies have suggested that FPV,
within a nearby region of several hundred nucleotides. On
which does not replicate in dog cells, could have jumped the
infection of the cell by an adenovirus or other helper, the
species barrier if as few as two amino acid changes occurred
AAV DNA is excised and replicates. Latent infection in
in the major coat protein VP2. Once the ancestor to CPV-2
humans appears to be common.
arose from FPV or a related virus, further selection for growth
Adenoviruses are the best studied helpers, and several
in dogs could have produced the virus CPV-2, which is much
regions of the adenovirus genome are involved in helper
better adapted to dogs as a natural host. Consistent with this
function, including E1A, E1B, E2A, E4, and VA. At least
hypothesis is the finding that antibodies to a CPV-2-like virus
some papillomaviruses can also serve as helpers, and in the
were first detected in serum from European dogs taken in the
case of HPV-16 the E1, E2, and E6 genes contribute to AAV
early to mid 1970s, but only in 1978 did explosive spread
replication. Replication of AAV downregulates the infec-
of the virus occur. Also of interest for this hypothesis is the
tion by HPV-16, which lowers the risk of cervical carcinoma
fact that a variant of CPV-2 called CPV-2a replaced CPV-2
induced by the papillomavirus. Retrospective studies have
between 1979 and 1981, and a newer variant 2b appeared in
found that patients with cervical carcinoma are markedly
1984. Since this time CPV-2a and -2b have changed little and
deficient in antibodies to AAV as compared with normal
appear to be in worldwide equilibrium.
controls. It is also known that independent replication of
A dendrogram of these various parvoviruses is shown
AAV in cultured cells can be obtained by treatment of the
in Fig. 7.36. Although CPV-2 is closely related to FPV and
cells with toxic agents such as UV or one of several chemi-
its relatives, it clearly belongs to its own clade, which shows
cal carcinogens. This treatment must induce the production
that the lineage of the canine virus is distinct. This is different
of cellular factors that are required for a full virus replication
from the pattern shown by the lineages of FPV and the viruses
cycle. The helper function supplied by the helper virus could
of foxes, mink, and other wildlife. Here the clades do not
then be to independently supply these factors or to induce
assort with species, which suggests that the various strains are
the production of these cellular factors. Thus, protection
freely transmissible among these various animals and circu-
from the development of cervical carcinoma by AAV could
late within this expanded group of species. Thus it is of inter-
be due not only to its effect upon the replication of papil-
est that CPV-2a and CPV-2b replicate well in cats, although
lomaviruses but also to increased replication in cancer cells,
CPV-2 does not. Also shown in the figure is a timeline for the
resulting in the death of the cell. AAV infection might there-
emergence of CPV and its divergence into the different lines.
fore protect against the formation of tumors and be a virus
that actually has a beneficial function in humans.
Genus Bocavirus
A recent isolate of a bocavirus from human respiratory
A new DNA-containing virus was isolated recently from
tract samples has been tentatively called human bocavi-
the blood of a Japanese patient and first called TT virus,
rus. The virus was subsequently detected in 17 humans and
after the initials of the patient, but subsequently renamed
appears to be associated with lower-respiratory-tract infec-
Torque teno virus. The viral genome was circular single-
tion in children. This may be a second parvovirus that causes
strand DNA, of size 3739 nucleotides. Studies of sera from
disease in humans.
other people around the world demonstrated that the virus
was widespread and common. Recent estimates are that
12% of Japanese, 1% of Americans, and 2% of English are
Genus Parvovirus
infected, but that a much larger fraction of the population
The genus Parvovirus contains viruses that infect a
in tropical countries such as Papua New Guinea (74% of
number of different mammals and birds. Several of these
people) and Gambia (83%) are infected. The nucleotide
cause important diseases in domestic animals or in wild-
sequences of different isolates from around the world
life, including feline panleukopenia virus (FPV), porcine
exhibit up to 50% sequence diversity, and in dendrograms
parvovirus, and canine parvovirus (CPV).
of these sequences the viruses fall into five different groups.
CPV is an example of an emerging nonhuman pathogen.
The viruses have been classified as belonging to the genus
It appeared suddenly in 1978 and spread around the globe in
Anellovirus. This genus was initially placed in the family
less than 6 months. The virus causes gastroenteritis in adult
Circoviridae but is now unclassified as to family.
Phylogenetic tree of the canine and feline parvoviruses
CPV - types
2a and 2b
CPV-Type 2
Isolated from:
Raccoon Dogs
Evolution of the canine parvoviruses
CPV type 2
Canine parvovirus
(emerged in Europe
in mid 1970's)
CPV type 2a
CPV type 2b
FIGURE 7.36  Phylogeny and evolution of feline and canine parvoviruses. Upper panel: phylogenetic tree of
parvoviruses from dogs (CPV), Asiatic raccoon dogs (RD), cats (FPV), mink (MEV), raccoons (RPV), and foxes
(BFPV), using porcine parvovirus (PPV) as an outgroup. The tree was constructed using the sequences of VP1 and VP2
and illustrates that all of the canine isolates form a distinct clade. Lower panel: diagram of the evolution of the canine
parvoviruses into the two types circulating today. From Parrish (1997).
The isolation of a new virus that is widespread and com-
TT virus was isolated from a patient with hepatitis. Thus,
mon illustrates that there may yet be other viruses that infect
a major interest in the virus is a possible association with
humans but of which we are unaware. Whether Torque teno
hepatitis in humans, but there is no evidence at present that it
virus or other viruses that are as yet unknown are associated
does cause hepatitis in humans.
with human disease remains to be determined.
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