From Stewart McNulty at Veterinary Sciences,
Queen's University, Belfast.
Are these viruses good for you? Maybe, but don't "dependo" on it!
The five serotypes of the human "adeno-associated
viruses" (AAV), belong to the genus Dependovirus. They earned the
name "Dependovirus" because they were believed to "depend" on coinfection
with an unrelated helper virus, such as adenovirus or herpesvirus, in order
to replicate. Although it has been demonstrated that these viruses
are not exclusively dependent on a helper virus and are capable of autonomously
replicating in the cell, they are still often referred to as Dependoviruses.
Adeno-associated virus infection is
very common throughout the world. More than 90% of adults are seropositive.
Most human transmission of AAV appears to be horizontal.
There is no evidence that associates
AAV with disease in any of its hosts, and it has no known tumor inducing
function. In the absence of a helper, a tandemly repeated double
stranded form of the AAV genome becomes integrated into the cellular genome
of its host. The virus persists in this latent form indefinitely
until a subsequent adenovirus infection reactivates AAV replication.
The question of the consequences to the host of latent AAV infection remains
unanswered, but the possibility that AAV infection may actually be beneficial
has been considered in terms of its possible ability to inhibit oncogenesis
of Adenovirus and Herpesvirus.
The genetic map of AAV is similar to
that of autonomous parvoviruses. Although long regarded as being unable
to replicate without a helper virus, it is now apparent that autonomous
replication of AAV is possible when cells containing AAV are treated with
any of several chemical agents that either synchronize cell division or
otherwise produce favorable growth conditions for the virus. Due to a number
of genetic properties, AAV has been given a significant amount of attention
as a possible vector for gene therapy. These properties include the
ability to integrate and establish a latent state with high frequency,
the lack of any associated known disease, and the fact that vectors can
be created with the use of few viral genes that will express protein products
on the surface of the transformed cell. In fact, such vectors
have been made and have shown promising results.
Could AAV infection be beneficial to its host? This question addresses
a fundamental dogma of virology, that basically claims that no viral infection
can be beneficial. Certain reports have shown that AAV reduces the
frequency of tumors and lengthens the induction times of occurring tumors,
in newborn hamsters. It has also been reported to inhibit oncogenicity
of HSV-II transformed cells after infection, which brings up the question
of whether AAV coinfection can benefit humans as well. In a retrospective
epidemiological study on patients with cervical carcinoma, the patients
were significantly deficient in antibodies to AAV compared to a group of
matched control. So who knows, maybe AAV infection is good for the host!
see reference #14 and #15
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