Category Archives: Evolution

Big Viruses for Small Hosts

Its a common misconception among my students that simpler hosts like bacteria or single celled eukaryotes would host simpler (ie smaller) viruses, but that is certainly not the case.

Another giant virus that infects a protist has been identified and sequenced. Like its close relative Mimivirus, this new virus called Cafeteria roenbergensis virus (CroV) has a very large genome and has many genes not typically found in viruses. Before the discovery of Mimivirus, viruses were not known to encode proteins involved in protein translation. That was a function on which viruses were totally dependent on the host. However, these giant viruses seem to have their fingers in protein translation too, showing us yet another strategy in manipulating host processes. There is also block of genes that appear to be derived from bacteria. The host species, C. roebergensis, eats bacteria, so it would be interesting to know if the bacterial genes were the result of a horizontal gene transfer event from a preferred host food.

Before CroV, all giant viruses identified infect amoebas. CroV infects C. roenbergensis, a marine protist. So what is it about protists that makes them good hosts for such big viruses? Why haven’t we found giant viruses infecting other eukaryotes?
Could the explanation lie in the still murky evolutionary origin of viruses? Another recent paper attempts to put some viruses (nucleocytoplasmic large DNA viruses, including giant viruses, poxes and herpesviruses) into the tree of life along with bacteria, archaea and eukaryotes. Using genes common to all, they showed that these viruses have a very ancient evolutionary origin, probably right around the time of the appearance of eukaryotes. Were the ancestral viruses more cell-like and over time progressively lost genes?


Should I Stay or Should I Go?

Some bacteriophages (viruses that infect bacteria) can undergo a special kind of replication cycle called lysogeny. Rather than making lots of new phages upon infection, these phages can pop their genome into the host chromosome. When the cell copies its DNA and divides, the integrated phage is copied too, so the daughter cells are infected. These integrated phages, or prophages turn out to be very important to us: cholera is caused by V. cholera bacteria with an integrated phage that expresses the toxin that causes diarrhea.
So what is the evolutionary advantage of the lysogenic/lytic switch for this phage? When would it “choose” one over the other? In my biol 105 class we discussed the evolutionary benefits of lysogeny. One of the most enjoyable parts of teaching is when students ask challenging questions that lead to fruitful discussion and deeper thought. Here is my perspective on this.
You can think of the lytic cycle as highly virulent (100% mortality) or lysogenic as non-virulent (no negative effect on the host while the phage is present as a prophage). Virulence is often related to transmission, such that viruses will evolve to have the optimal level of virulence to allow for efficient transmission. Since lysogenic phages can switch between high and low virulence, when would high virulence be favored for transmission and when would low virulence be favored?
A highly virulent pathogen runs the risk of wiping out its host population. If the cells are growing actively in an environment like the gut, and the virus is replicating to high levels, it could spread to the entire host population eventually killing every cell. The virus would then depend on either more V. cholera entering the gut, or getting out of the gut and spreading to a new human host infected with cholera. Alternatively, cholera can also grow in the environment, so the phage could infect a cell in the environment. However there is some obvious risk there, that of finding the next host cholera cell either in a gut or the environment. Its a big world out there for a tiny phage and a tiny bacterial cell to meet each other. A less risky approach might be to limit virulence and allow prophage infected cells to survive. The cholera cells will be returned to the environment, where they can replicate or to a new human host where it can also replicate. Either way, the phage is guaranteed to find a host, because its already in it.
Now if the prophage finds itself in cells that are no longer growing, there may be an advantage to getting out and finding “happy” hosts. Cells that are not growing could be at greater risk of cell damage and death, perhaps they are not acquiring the nutrients and energy necessary to grow or repair cellular damage. If the cell dies, the phage will not be able to replicate. So the phage would enter the lytic cycle and release progeny. The risk of not finding a new host would presumably be lower than the risk of staying within a dying host. High virulence therefore is advantageous for transmission in this situation.
Does anyone have a different perspective?


1918 and 2009

The 1918 influenza pandemic (the “Spanish Flu”), by some estimates, killed as many as 100 million people in a very short period of time.  The 2009 “Swine Flu” pandemic didnt kill so many, but it spread rapidly and widely across the globe.  Despite that difference, it turns out the two viruses responsible for these pandemics have some important similarities.

Influenza virus has a protein on the surface called hemagglutinin, or HA, which is used to attach to host cells, allowing the virus to then enter and replicate.  HAs change rapidly, which is partly why influenza keeps coming back.  When HA changes, your antibodies dont recognize it so well, so you get sick again.  It turns out that the HAs of 2009 and 1918 are similar on both the sequence and structure level.  There is a small patch on the HA protein that is 95% identical between 1918 and 2009 but only 70% identical to seasonal strains.  Looking only at the 3D structure, among all influenza HAs, the 2009 HA is most similar to the 1918 HA.  The 1918 and 2009 HAs also lack glycosylation at the tip, while seasonal influenza viruses HAs are sugary.

Why is that interesting? An unusual pattern was noted in the 2009 pandemic: elderly people were not as affected as younger people, the reverse of what is usually seen with influenza.  It was proposed that perhaps some people still had immunity to the 1918 virus, which continued to circulate for many years after 1918, and that immunity was cross-protective.  A recent study shows that this indeed seems to be the case.  Mice immunized with the 1918 virus are protected against the 2009 virus.  The converse is also true: if you immunize mice with the 2009 virus, they are protected against the 1918 virus.  That’s pretty impressive when you consider that one season’s vaccine might not protect you from next season’s virus. It seems the immune system cant really tell the difference between these viruses.  Note that it also tells us how long immunity can last!  The next question is, how and why has this HA structure come back?


Distant Evolutionary Relationships

We’ve been talking about protein structure and folding in my Biol 105 class.  Proteins are made of chains of amino acids and the sequence of amino acids, or primary structure, dictates the way the protein will fold into its final 3D or tertiary structure.  We may assume that two proteins with similar sequences would have a similar structure, and that two proteins with very different sequences would have different structures.  However, this is not true.  Proteins with very different sequences can end up with similar 3D structures.

A great example of this is the structure of capsid proteins from three very different viruses.  Adenoviruses infect animals (eukaryotes), and is one of many viruses that cause colds.  PRD1 is a bacteriphage, a virus that infects bacteria.  STIV (Sulfolobus turreted icosahedral virus) infects Sulfolobus, an archaea that lives in geothermal hotsprings in Yellowstone National Park.  STIV and its host love the 80 degree celsius, pH 3 environment of the hotsprings.  The fact that there are viruses that infect archaea in those extreme environments is cool enough.  But it turns out that the capsid proteins of these three viruses are actually quite similar.  Their sequence differs significantly, but their tertiary structures are highly similar, meaning these very different polypeptides fold into essentially the same shape.

What is the basis of this similarity?  Do all theses viruses share a common ancestor, which would have existed before the three domains of cellular life (eukarya, bacteria, archaea) diverged over 3 billion years ago? Is it convergent evolution?  Was there a horizontal gene transfer event in which a gene moved among all three domains?  The authors of the paper argue for a common ancestor but the other possibilities have not been formally excluded.  We still don’t really know, and it raises interesting questions about the origin of viruses.


Monkeypox and Herd Immunity

In 1980, smallpox was declared eradicated following an intensive global vaccination campaign.  The virus, Variola, has some close relatives that can infect humans, one of which is monkeypox.  Monkeypox isnt nearly the problem that smallpox was; it has a much lower mortality rate and outbreaks tend to fizzle out quickly due to poor human-to-human transmission.

However, a recent paper suggests that monkeypox infections are becoming an increasing problem.  So why is it emerging now?  Its a problem we’ve been anticipating, actually.  Turns out that when you get the smallpox vaccine (or smallpox itself), it also protects you from monkeypox.  So pre-eradication, most people were immune to monkeypox.  If you met up with an infected animal, chances are you were immune and wouldn’t get infected.  If you did somehow get infected, chances are most people around you were immune so you couldn’t transmit it to others.  An immune host is not fertile ground for viral replication, so whenever immune hosts are encountered, the chain of viral transmission ends.  In fact, a highly vaccinated population helps those few individuals that are not vaccinated by greatly limiting the potential of the virus reaching the unvaccinated (“naive”) individual.  Thats called herd immunity.

Turns out herd immunity to smallpox, and therefore monkeypox, is waning.  Vaccinations stopped in 1980 so anyone born after that is naive and therefore there is a major lapse in herd immunity.  Risk of infection with monkeypox virus is now as much as 20 times greater than 30 years ago.  Interestingly, all those old people born before 1980 who were vaccinated have a much lower risk of infection, telling us that immunity from vaccination lasts 30+ years.

So why should we worry about waning herd immunity to a rare and relatively mild disease that is hardly contagious?  Well, variola and monkeypoxviruses are about 96% identical.  We dont know how much  monkeypox needs to mutate to become sustainable in humans or more virulent.


Have Fun Storming the Castle!

One of the things that I find most interesting about viruses is the diversity in their replication cycles.  It seems that for every barrier that viruses encounter during replication it is overcome in a myriad of ways.

Imagine you are a warrior invading a castle.  How many different ways can you penetrate the defenses, cross the moat, get through the walls, and then access and use all the stuff inside for your own benefit?  Will you knock down the gate?  Will you sneak through the windows?  Catapult yourself over the wall?

A Virus must enter a host cell, take over the machinery to make lots of copies of itself, then get out and transmit to the next host.  While the viral replication cycle of all viruses follows the same general patterns, the subtle differences are fascinating.  Its like an evolutionary brainstorm that resulted in thousands of different ways to solve the same basic problem.

Ive asked my Biol 105 class to read Ch 19 of Campbell’s Biology and post a comment about an interesting thing about viruses that caught their attention.  DId you learn something new and surprising?  What is it about it that is interesting to you?


Viruses: Dead or Alive

An ongoing question in virology is whether viruses are to be considered living creatures.  Its easy to tell that a groundhog is alive but a book is not.  But what properties does a groundhog have that a book does not?  We can look up basic properties of living things in a biology textbook, and yet it remains difficult to define life in a simple sentence.

I would argue that a virus is not alive. Viruses are completely dependent on host cells to replicate.  That said, in absence of the host cell the virus clearly lacks most of the properties of a living thing.  (Does stealing those properties from a living thing count towards being alive?)  Life seems to emerge from a collection of parts where the whole is greater  than the sum of the parts.  This emergent property, life, is present in animals, plants, bacteria etc, but in a virus infected cell, that property remains a part of the cell, not the virus.

Alive or not, viruses are an integral part of biology.  They help us understand life and they certainly have an effect on living things.