Monthly Archives: September 2010

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TWiV Podcast

TWiV: This Week in Virology.  I love listening to this podcast.  When people see me listening to my iPod, they may think I’m cool and listening to the hip music all the kids are listening to these days, but no, I’m being nerdy and listening to a bunch of scientists talk about viruses.  Its a great resource for learning about virology and just listening in on discussions among scientists gives you a good sense of how science proceeds – lots of questions and curiosity about the world around you.

You can go to the website or download podcasts from iTunes.

http://www.twiv.tv/

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Molecular Virology

Ebola Virus Entry

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Viruses can enter cells through a variety of different pathways.  Many enter through endocytosis, and there are actually several endocytic pathways: clathrin mediated, caveolin mediated, phago- and pinocytosis, and the rather mysterious “non-clathrin, non-caveolin mediated endocytosis.”

Ebola virus causes a severe hemorrhagic disease with 90% mortality.  Its an obviously frightening virus which makes it difficult to study, but knowing the details of its replication cycle may provide important clues on how to treat or prevent the disease.  A recent paper demonstrates that Ebola probably uses clathrin-mediated endocytosis.  Clathrin is a protein that forms a polyhedral lattice on the inside of the cell membrane helping to form vesicles.  Virus attachment induces this vesicle formation, giving the virus access to the cell by entering through these vesicles.  Among other experiments, they found that if you use the drug chorpromazine, which inhibits clathrin function, you can block Ebola entry.

The paper raises some interesting questions. First, they didnt actually use Ebola virus.  They used a modified HIV that expresses the Ebola virus glycoprotein involved in attachment and entry.  Does the natural virus enter in the same way?  They used several different cells in culture and found clathrin dependence in all of them, but is it the same in an infected animal?  Finally is the drug chlorpromazine one that could be used clinically?  Presumably not since disrupting clathrin mediated endocytosis would probably have a broadly toxic effect on the host, but it is an interesting lead compound.

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Evolution, Molecular Virology

Distant Evolutionary Relationships

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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.

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Epidemics, Evolution, Immunology

Monkeypox and Herd Immunity

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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.

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