Wednesday, March 5, 2014

Resurrected 30 000 year old virus provides clues for viral diversity

By now lots of people have probably heard the news about the 30 000 year old virus from the Russian Arctic that was discovered and brought back to life.  A group of scientists from France initiated a survey of the Siberian permafrost, and discovered a large DNA virus that maintained its ability to infect its host after thawing.  Reports have been clear about the fact that this virus does not affect humans or animals.

We all know of viruses that affect humans, like influenza and varicella, but people may be more unfamiliar with giant viruses.  Large DNA viruses are viruses that contain DNA, and whose particles are large enough to be seen using a light microscope (the ones we all used in high school).  Considering that most bacteria are 1/10th the size of bacteria, that makes these large viruses huge!  Virus particles (or virions) contain genetic material (either DNA or RNA), a protein coat to protect the genetic material, and an envelope around the protein coat. (x).
There is debate as to whether or not viruses can be considered "alive".  They do carry their own genetic material, they reproduce, although they need a host cell to do it, and they are able to evolve (that's why antiretroviral drugs for HIV treatment that worked well in the last decades don't work as well anymore).  What keeps them from truly being classified as "alive" is that they lack key characteristics such as cell structure.  Viruses are often described as organisms on the edge of life.

 Regardless of the type of virus you're dealing with, the life cycle will be the same.  Viruses attach themselves to a host cell and releases its genetic material inside.  That genetic material essentially hijacks the host cell's enzymes to make more viruses.  The viral particles assemble into viruses, which eventually lyse, or split, the cell.  Proteins are classified by what type of genetic material they have, and which enzymes they take over in their host cell.

DNA viruses carry DNA as their genetic material.  One example of a DNA virus is varicella, or chickenpox.  This type of virus hijacks DNA polymerase, the enzyme that copies and replicates DNA, and is used in cell division.  I wrote a bit about DNA polymerase in relation to telomere erosion last month.  Basically, what happens is the enzyme copies the DNA from the virus, which is then copied into RNA like the rest of the host cell's genome.  Influenza is an RNA virus.  That means that its genetic material is RNA.  The classification system for RNA viruses is a bit more complicated than I want to get into.  The simplest way to think of it is this: in our cells, DNA is transcribed into RNA, which is then translated into proteins.  For RNA viruses, their genetic material enters the cell as RNA, so it hijacks the translation enzymes, or the enzymes that are used in making proteins.  In a sense, RNA viruses skip one of the steps that DNA viruses use.  There are also retroviruses, such as HIV, which is also an RNA virus, but the difference is that it requires the reverse transcription of RNA into DNA.  The virus has its own enzyme that does this (called Reverse Transcriptase - scientists are creative!), the resulting DNA is then incorporated into the host genome.  Then the host cell treats the viral DNA like its own DNA, replicating it and making lots of viral particles.  Viruses are a really important means of horizontal gene transfer, the process of transferring genes from one organism to another by a means other than reproduction.  As such, viruses are an important contributor to genetic diversity.

The large DNA virus that was found in the Siberian permafrost infect a type of protist of the genus Acanthamoeba.  These are a type of amoeba that are most often found in fresh water.  The amoeba are mostly bacterivores, which means they eat bacteria, but some opportunistically infect humans and animals too.  The researchers found the large DNA virus, called Pithovirus sibericum, by using Acanthamoeba as bait.  The Pithovirus was then identified using a light microscope, and was collected from deep permafrost layers, whose oldest sediments date back to the Pleistocene, which ranges from 2.5 million to 11 000 years ago.  The sediments in which Pithovirus was found are 30 000 years old.  The virus was used to infect Acanthamoeba in order to amplify viral particles, which were then observed.  That means that the virus was still able to infect its host cell (aka, still virulent) even after 30 centuries!  The researchers were able to look at a full replication cycles, which lasted around 10-20 hours.                                           
There are other types of large DNA viruses that have been identified that infect Acanthamoeba.  They are Mimivirus, Moumouvirus, Megavirus, and Pandoravirus.  Prior to the discovery of Pandoravirus, large DNA viruses displayed the same distinctive features: they all had similarly shaped and sized capsids (the protein coat surrounding the genetic material), a large, adenine-thymine (AT)-rich genome, and they encode their own full transcription mechanism.  Pandoravirus shook things up with its large amphora-shaped capsids, and its cytosine-guanine (CT)-rich genome.  It basically has no resemblance to the other large DNA viruses.  So it was believed that large DNA viruses that infect Acanthamoeba were segregated into two families.  The discovery of Pithovirus now shows that large viruses are more diverse than originally thought.  DNA sequencing of Pithovirus found an AT-rich genome that is remarkably small, about 5 times smaller than that of Pandoravirus.  The genome of Pithovirus also encodes 5 times fewer proteins than the genome of Pandoravirus, although interestingly, the number of proteins that are used to make viral particles are similar between the two types of virus.  That pretty much means that large and complex  viral particles don't necessarily always have to come from larger genomes.  

The authors mention that this is the first time an ancient virus like this has been revived.  There have been other ancient viruses identified, ranging from 7000-140 000 years old, but no mention has been made of their viability.  The authors also stress that the thawing of the Siberian permafrost due to climate change, drilling, or mining, may cause the release of ancient and viable pathogens like Pithovirus that we're not ready to deal with.  Pithovirus may not infect humans, but it has a genome structure and replication cycle similar to that of other large DNA viruses that do infect humans and animals, and their release into our ecosystem could have devastating effects on human health.

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