- Digging deep into their reproductive machinery, scientists
have found startling evidence that broad classes of viruses - including
those that harbor the agents that cause such diverse ailments as AIDS,
the common cold and hepatitis - share functional traits that suggest they
all evolved from a common ancestor.
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- The discovery, reported in the journal Molecular Cell,
unexpectedly unites half of virology, linking large groups of viruses long
thought to be functionally and evolutionarily distinct. The finding could
well speed the search for vaccines and treatments for a wide range of virus-related
ailments that plague both people and animals.
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- "Recognition of these links means that principles
learned from a variety of virus systems now can be used to illuminate many
others, allowing integration and generalization of knowledge across a wide
range of important pathogens," says Paul Ahlquist of the Howard Hughes
Medical Institute at the University of Wisconsin-Madison.
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- Ahlquist, the UW-Madison Kaesberg Professor of Molecular
Virology and an author of the study, says the new results show that the
viruses that cause ailments as distinct as the common cold, West Nile,
hepatitis C, foot and mouth disease, and many others are functionally and,
likely, evolutionarily related to HIV, the virus that causes AIDS.
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- The finding is a surprise because many of the viruses
responsible for these illnesses were thought to reproduce in ways so different
from one another biologically that they were long believed to be unrelated.
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- All viruses belong to any of six major classifications.
Each class differs in important and fundamental ways, and each appears
to represent major evolutionary lineages, Ahlquist says. "In each
of these classes, there are important pathogens, and in each of these six
classes there is lots of different biology."
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- Working with a much-explored model virus, Ahlquist and
co-authors Michael Schwartz, Jianbo Chen, Michael Janda, Michael Sullivan
and Johan den Boon, all of the UW-Madison Institute for Molecular Virology,
show that key features of replication run parallel in three of the six
broad classes of viruses. It turns out, says Ahlquist, that while the viruses
in these three groups build different structures to move between host cells,
basic mechanisms in their replication seem to be the same.
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- Although diverse, viruses as a rule are relatively simple
organisms composed of genetic material - RNA or DNA - packed inside a protein
coat. Their goal is to reproduce and pass along their genes using the reproductive
machinery of the cells they invade to make virions, infectious particles
that act like seeds to infect other cells.
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- The parallel features discovered by the Wisconsin team
involve the mechanisms by which viruses replicate their genetic information
after they commandeer the cells of the hosts they infect.
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- Some viruses related by these findings replicate by switching
their genes between RNA and DNA, while others store and replicate their
genes only as RNAs. However, one newfound commonality among these viruses
is that during replication, each passes its genome through an intermediate
stage of a particular kind of RNA - messenger RNA.
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- "This viral messenger RNA has two distinct functions,"
Ahlquist explains. "It is used by normal cellular machinery as a template
to synthesize viral proteins, and by virus-induced machinery as a template
to replicate the viral genome."
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- A second common feature found by the Wisconsin team is
that this viral genetic template, the messenger RNA, always becomes sequestered
within a compartment generated within newly infected cells by the invading
virus. "This new virus-induced compartment, in which the virus genome
is reserved and copied, shows surprising similarities across these different
virus groups."
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- On the surface, the reproductive workings of viruses
are extremely complicated as, over time, they have evolved subtle and intricate
ways to camouflage themselves or otherwise circumvent the immune defenses
of their hosts. Finding common threads, says Ahlquist, means it is possible
to generalize knowledge across broad classes of viruses.
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- The three major virus groupings of viruses that showed
this surprising affinity are:
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- * Positive strand RNA viruses, which includes cancer-causing
hepatitis C, viruses that cause the common cold and many others.
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- * Reverse transcribing viruses, which include HIV, the
virus that causes AIDS.
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- * Double stranded RNA viruses, a grouping that includes
rotavirus, a virus that kills about one million children a year in developing
countries.
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- These three groupings encompass over half of the world's
known virus families. Finding commonalties on such a grand scale bolsters
prospects for the development of broad-spectrum antiviral agents.
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- "These results have added considerably to our understanding
of these viruses, and any new basic knowledge is useful in control,"
Ahlquist says. "If you know the machinery, you know where to throw
the wrench to mess it up."
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- Note: This story has been adapted from a news release
issued by University Of Wisconsin-Madison for journalists and other members
of the public. If you wish to quote from any part of this story, please
credit University Of Wisconsin-Madison as the original source. You may
also wish to include the following link in any citation:
-
- http://www.sciencedaily.com/releases/2002/03/020326073145.htm
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