A few good viruses

A few good viruses
7 February 2007
by Hamish Clarke
Cosmos Online

Viruses generally get a bad rap, but in laboratories around the world, these miniscule hijackers are themselves being hijacked to treat some of humanity’s most feared diseases.

As far as words with negative connotations go, it’s hard to top ‘virus’. AIDS, bird flu, cholera, Dengue fever, Ebola – and that’s just the first five letters of the alphabet. And when Agent Smith tells Neo in The Matrix that he considers the human race a virus, it’s widely understood that he’s not paying a compliment.

But for a rising number of scientists, viruses aren’t sinister at all. Instead, they are at the forefront of the latest advances in genetic technology, bringing hope to those with previously incurable diseases.

Hitchhikers, hijackers & hosts
Defining viruses is notoriously difficult. Though viruses are a subject firmly rooted in biology, ask a biologist for an explanation of what they are and you’re likely to hear some emphatically non-biological descriptives like ‘particle’, ‘entity’ and ‘fragment’.

Like some bacteria, and even ‘higher’ eukaryotic organisms such as fungi, viruses are entirely dependent on a host organism for survival. But unlike the others, viruses are not generally afforded ‘living’ status because they consist of little more than DNA or RNA wrapped in a shell, without the tools for reproducing themselves or turning their genetic information into useful proteins.

When a virus infects a host cell, the cell becomes its workshop. It hijacks the machinery of the cell, turning it from its usual purposes to the sole task of replicating the virus’s genetic material and protein coat. So effectively does the virus take over the cell – so many copies of the virus does it produce – that the cell eventually suicides, bursting under the pressure of the viral progeny (also called bicentuplets), setting them free to infect other cells and continue the cycle.

But there is another path the virus can take, one that has spawned a research love affair with viruses. Rather than immediately hijacking the cell for its own reproductive ends, sometimes a virus will insert its genes into the host’s genome, ensuring their safety and biding its time until conditions are right for replication. Often this is not harmful to the host cell, and during this period of dormancy the viral DNA gets replicated along with the rest of genome when the cell divides. Eventually, a trigger may activate the viral genes, which usurp control of the cell’s machinery and send off daughter viruses to infect other cells.

Tool thief or tool?
In 1952, Martha Chase and Alfred Hershey used viruses to help establish that DNA, rather than protein, forms the basis of heredity. Cheap, quick to produce, and easy to modify, a core group of viruses has filled out the toolboxes of many a biologist ever since.

Their ability to entwine themselves with the host’s genome has made viruses the darlings of the field of gene therapy. The once outlandish scenario of going into a person’s cells and correcting genetic ‘typos’ is now an earnest aim of researchers, who hope intentional viral infections will one day help sufferers of diseases such as Parkinson’s and Severe Combined Immunodeficiency (SCID), also known as ‘bubble boy syndrome’, a mutation in the genome that prevents the body’s immune system from functioning.

Researchers plan to ‘hijack the hijackers’ – swapping the virus’ harmful genes for a corrected version of the patient’s defective genes and using the virus’ unique abilities to insert the gene into patient’s genome. In reality, the procedure is fraught with difficulties, not least getting the right amount of gene in the right location without side effects.

Pavel Osten from Northwestern University in Chicago, Illinois, recently co-authored a paper on the use of viruses as DNA delivery systems, or vectors. “In my view, it is most likely that this work [gene therapy] will become a mainstream treatment of some of the devastating brain disorders for which there is currently no treatment,” he wrote.

But how would you feel about being injected with a virus to cure a disease? According to Osten, the risks are low and decreasing. “The viral vectors … are in most cases stripped down to the most basic elements that are required for gene delivery, and thus in no possible way pose any risk with respect to the original disease.”

Viruses don’t attack only animal cells, however. The vast majority of viruses actually target bacteria, including the bacteria that infect humans; they are called bacteriophages, or phages for short (from the Greek phagein, to consume). “For years researchers have been looking at using this targeted bacterial killing as an alternative to antibiotics,” says Jason Clark from Moredun Research Institute in Scotland. While this might seem a bit like inviting in the barbarians, it’s also sound science; in August of last year, the U.S. Food and Drug Administration (FDA) approved a bacteriophage food spray designed to reduce the amount of illness-causing bacteria on ready-to-eat meals.

It’s a virus’ world
By probing their workings and exploiting their functions in laboratories around the world, scientists have gone a long way toward demystifying viruses. But recent revelations about the extent of viral diversity could radically shift our perceptions of them again.

The advent of a range of DNA-sequencing technologies has allowed microbiologists to move beyond the constraints of studying only what they can culture in the lab, and glimpse what exists ‘out there’ – in the soil, in the sea and in our guts. And the results have been eye opening. According to some estimates, the total number of viruses exceeds the total number of cells in every other life form – including bacteria – by a factor of ten. “The total biomass and biodiversity of viruses is truly staggering,” says microbiologist Nick Coleman, from the University of Sydney in Australia.

So what are all these viruses doing? Should we be avoiding contact with other people and frequently sterilising ourselves? According to Coleman, viruses actually do a lot to control other parasites. “The implication [of microbial biodiversity studies] is that most, if not all, larger microbes are subject to viral parasitism, and that viruses might be crucial in controlling the populations of other microbes.”

Forest Rohwer of San Diego State University in southern California has conducted several landmark studies of marine microbial diversity. Rohwer has seen a change in attitudes towards viruses over the years. “Scientists have always recognized the importance of viruses, but recently it has become clearer that viruses are an integral part of every ecosystem and can’t be ignored when we try to understand how life on Earth works,” he says. “We usually only hear about viruses in the context of human disease. But most viruses are actually not harmful, and in fact have played an important part in evolution and in maintaining healthy ecosystems.”

Andrew Holmes, a microbiologist from the University of Sydney, thinks that people should know that “viruses are everywhere and do not instantly equal ‘bad’… [they] have the potential to cause very rapid biological change through epidemic disease, but that is exceedingly rare,” he says. “Vigilance is important but panic is unwarranted.” Holmes points out that this same process is an important part of correcting imbalances that occur in nature. For example, one mechanism by which algal blooms – explosions of algae that choke sea life and disrupt food chains – break down is viral disease. As Holmes puts it, “such viruses are the means by which the ecosystem corrects itself.”

According to Rohwer, when you multiply the number of viruses out there by the billions of years they’ve been around, their probable influence over evolution is huge. “They are able to move genetic information between different hosts, but we still do not fully understand how this has influenced, and continues to influence, the evolution of new species.”

So the next time your nose starts to run or you feel a tickle in your throat, spare a thought for your uninvited guest … and the role you play as gracious host to a galaxy of hitchhikers.

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