Category Archives: Evolution


Most viral infections start out with the same general symptoms: fever, malaise, aches. Those are usually the sign of your immune system starting to fight back. Fever is one of our defense mechanisms, and while it can be quite uncomfortable it is very rarely dangerous. One of the common questions I get asked in my classes is whether it is good or bad to take fever reducing medicines when you are sick. Well, Im not that kind of doctor so I can’t really answer that question, but I can tell you what research has been done on the benefits of fever.

The adaptive value of Saturday Night Fever, caused by listening to Disco, remains unknown

Presumably, by raising your body temperature, you can do a better job of fighting off an infection. The higher temperature may make it more difficult for the pathogen to grow because it grows optimally only at normal body temperature, or it may help the immune system work faster (or both). Some studies in animals have shown that reducing fever results in increased growth of bacteria or virus in the infected animal, and other studies have found increased proliferation, migration and activity of immune cells.

Whatever the mechanism, it is clear that fever must provide some advantage. There are many studies that demonstrate that fever is beneficial in overcoming infection. None of these studies alone is definitive, however taken together, they do seem to support a role for fever in fighting infection. For one, the febrile response is highly conserved in vertebrates (even “cold blooded” animals) and many invertebrates. Some lizards, for example, will seek warmer spots to rest and as a result, raise their body temperature when infected. Fever is also energetically very expensive, requiring 20% more energy to maintain a temperature even a few degrees above normal. It would be unlikely for such an expensive mechanism to be maintained by natural selection if it didn’t have some benefit.

In addition to the evolutionary perspective, several studies in animals show that a fever of a few degrees correlates with better survival rate from infection. Being correlations, we must be cautious in over-interpreting this. Another good way to test if something like fever is useful is to get rid of it. Infected animals can be treated with anti-pyretic (fever reducing) drugs to see what happens to their recovery in the absence of fever. These studies typically show that animals treated with anti-pyretic drugs take longer to recover, and in some cases even to increased mortality. There are some problems with anti-pyretic studies however, and one of the major problems is that many anti-pyretic drugs don’t just reduce fevers. They can have other effects on the body, not all of which are known, and so we can’t always be certain that fever reduction is the reason for the changes in morbidity and mortality.

Of course, I also like to look at the pathogens themselves for hints of what our immune system is doing. They are pretty good at defending themselves against our immune response, so if we look at their defenses we can learn more about how we attack them. The poxvirus Vaccinia encodes a protein that blocks fever. This protein interferes with the function of interleukin-1B, a component of our own immune system that regulates fever. Animals infected with Vaccinia lacking that protein develop fever, showing that when the viral protein is present, the virus can prevent fever. However, interleukin-1B does many other things too, not just regulation of fever, so it is possible that the virus is blocking interleukin-1B for a different reason.

So it is highly likely that fever is good for fighting off infections, but this is not to be taken as medical advice to avoid fever reducing medicines. In the case of naturally occurring infections in humans, we need much more research into fevers resulting from specific infections to decide when a fever is beneficial and should be left alone, whether the fever is dangerous, or if the fever is helpful but the risks of taking an anti-pyretic are worth alleviating the uncomfortable symptoms.

Kluger, M.J. (1996) The adaptive value of fever. Infectious disease clinics of north america. 1(10):1-20.
Alcami, A. and Smith, G.L. (1996) A mechanism for the inhibition of fever by a virus. Proc Natl Acad Sci. 93:11029-11034.


Giant dsDNA Virus Origins: Megaviridae Evolutionary Analysis

Contributed by guest blogger: Katy Hwang ’12

The discovery of the double stranded DNA (dsDNA) virus, Mimivirus, and the subsequent discovery of related Megavirus confounded the size limits of viral particles and the complexity of viral genomes. They are larger or just as large as some bacteria. Megavirus has a 1,259,197-bp genome.  Megavirus contains a genome 6.5% larger than that of Mimivirus. Each of these viruses, classified as Megaviridae, have approximately 979+ proteins, including the first aminoacyl tRNA synthetases (AARS), enzymes that promote translation, found outside of cellular organisms.

Mimivirus infects amoeba; Megavirus natural host is still unknown as it was found in a sea water sample through a campaign on random aquatic environmental sampling off of the coast of Las Cruces, Chile. Megavirus research is conducted in A. castellanii. The virus even reopened the debate on whether or not viruses are alive as Megaviridae have traits that overlap with unicellular organisms such as parasitic bacteria. Phylogenic evidence does not cluster either virus into a prokaryotic clade, but more deeply into a eukaryotic clade. Megavirus is of the archeal type, so it branched out before the radiation of eukaryotes. This provides some insight into the Megaviridae ancestor.  So now the question is: from what did these giant viruses originate and  how did they evolve?

Megavirus and Mimivirus are similar enough to have unambiguous homologous features, but have also diverged enough on the evolutionarily tree to provide more information on the features of a common ancestor. 23% of the Megavirus genome does not have a counterpart in Mimivirus, but it shares about 77% of its 1120 putative coding sequences with Mimivius. Megavirus and Mimivrius use the same motif to specify early gene expression, the expression pattern of the orthologous genes is conserved globally. Not only do these giant viruses have their own AARS, but they also code for their own DNA repair enzymes that correct damage caused by UV light, ionizing radiation and chemical mutagens. Megavirus also has a DNA photolyase, which is an enzyme that uses light energy to make repairs to DNA and increases resistance to UV radiation.

The author’s hypothesis is that the last Megaviridae common ancestor originated from a cellular organism, where the now current Megaviridae have undergone specific genome reduction events. Mimivirus codes for four AARS and Megavirus codes for seven, four being orthologs to those found in Mimivirus and one of the other AARS that Megavirus codes for is a class-II AARS. This observation that viral AARS are not limited to type-I suggests that independent acquisition of these genes by horizontal gene transfer is unlikely.  The ancestor of Megaviridae and Mimivirus most likely started with 20 AARS from a cellular ancestor. It is very unlikely that these seven coding sequences were added, and more likely that there were various lineage specific gene family deletions.

The discovery of the AARS substantiate the claims that the Megaviridae ancestor originated from a cellular organism.  What were the driving factors of these genome reduction events?  More etiological data is required for further analysis of the evolutionary process of the development into these giant dsDNA viruses. What other giant viruses are still out in the world waiting to be discovered and what can we learn from them?



Katy Hwang is a senior at Vassar College, majoring in biology.


H5N1 Ferret Transmission Experiment Published

At last, one of the papers investigating H5N1 influenza transmission in ferrets has been published in the journal Nature yesterday.  To recap the controversy briefly:  news of experimental studies investigating transmissibility of avian H5N1 influenza hit the news this fall, igniting a fierce debate about biosecurity, “dual use” research, and the damage that censorship can have on scientific advancement.  An advisory group, the NSABB, recommended partial censorship of the data, perhaps believing that redacting specific data from the publications would prevent information on how to generate a highly pathogenic mammalian transmissible virus from getting into the hands of bioterrorists or others incapable of handling such viruses safely.  However, after some new data or clarification of data presented in a revised version of the submitted manuscript, the NSABB recommended publication in full.

Avian H5N1 influenza virus has caused sporadic infections in humans who have close contact with infected animals.  Human-to-human transmission has not been observed.  But could an H5 virus mutate or reassort, allowing human-to-human transmission?

One thing that has been lost in this whole controversy is that this study is actually a great demonstration and application of evolution.  How does a virus switch to a new host and transmit efficiently between individuals?  Start with a diverse population that varies in a particular trait (in this case, ability to bind the human receptor).  Put it through selective pressure. This occurred in several steps: first, select for viruses that can bind the human receptor in vitro.  From those that bind, select ones that can efficiently replicate in the respiratory tract of the animal.  Finally, take the efficient replicators and allow for transmission.  At each step of selection, mutations that naturally occur during viral replication further diversify the population resulting in variants that possess the desired property.  Those variants get selected for the next experiment.

This study focused on one particular influenza virus protein, hemagglutinin (HA).  HA is on the surface of the virion and is what the virus uses to attach to the host cell, the first step in viral infection.  HA of human influenza viruses bind a sugar on the surface of human cells, which is slightly different from that found in the avian respiratory tract.  Avian viruses, of course, bind to the form found in birds.  H5 shows a strong preference for binding the avian receptor, so Karaoka et al were interested in finding out if H5 could change to recognize the human receptor, allowing more efficient transmission between mammals.

To address this, they began with a mutagenesis technique to introduce random mutations in the globular head (the receptor binding part) of HA, then used an in vitro approach to select for mutants that bound the human receptor (selection step 1).  Through this process they identified three H5 variants that gained the ability to bind the human receptor while maintaining the ability to bind the avian receptor, and one that switched specificity completely to the human receptor.  Several of the mutations identified in this study had already been shown in previous studies to be important in receptor specificity.

To test if the variant H5s conferred binding to human receptors in vivo, sections of human tracheal tissue were exposed to the viruses and only two were able to infect (selection step 2).  This suggests the virus can infect human epithelium of the upper respiratory tract.

Next, the two remaining variants were used to infect ferrets.  Both replicated in ferret respiratory tracts, but one replicated to higher levels.  When they sequenced the virus that they isolated from that ferret, it was different from what they had put in: a new mutation had appeared.  This new mutation presumably confers the property of better replication in the ferret respiratory tract, so it outgrew the original input virus (selection step 3).

Using this new virus (now with a total of 3 mutations in H5), transmission was tested in ferrets.  Compared to the original H5, which did not transmit via aerosol, the 3-mutation variant did transmit, although between only 2 of 6 animal pairs.  Again, they sequenced the virus that was present in the contact animals and found that it was different than what had gone in to the inoculated animals.  Yet another mutation had appeared (selection step 4).  This additional mutation appears to enhance transmission:  the new virus, now with 4 mutations, transmitted more quickly and between more pairs of animals than the 3-mutation virus.  Although the virus can transmit, none of the infected animals died, but they did show pathology at the site of infection.

So what does this all mean? The best model available for influenza transmission studies is ferrets.  Ferrets aren’t humans, so its important to keep in mind that this is a model that helps us understand what viral or host factors are involved in aerosol transmission in these mammals, and maybe, but not necessarily, in humans.  Since we don’t know what is necessary for human-to-human transmission, it is valuable to have an animal model to give us some ideas of what to look for.  It can provide some good hypotheses on what mediates transmission in humans, which would then have to be further tested.  Obviously, specificity for the human receptor is necessary, but the mutations identified tell us more than that.  Mutations that change specificity are not sufficient for transmission.  It turns out that those mutations also decrease the stability of the HA protein.  The additional mutations acquired through the selection steps compensate for that, and enhance stability.   So now we know that HA stability is important in influenza transmission.  Between ferrets.  That’s probably true for humans too, but it would need to be tested.

If you are still reading, you are obviously procrastinating, and are probably avoiding studying for your final exam.  But here are some more thoughts on the controversy overall.  This is a really interesting paper, with nothing particularly frightening or worrisome about it.  Certainly not any more so than other papers doing similar work that were published without so much controversy.  If “dual use” research needs to be regulated, it needs to be done before the work is done, not after.  If the NSABB was concerned about this kind of research, why only express concern once the experiment succeeds?  In my intro biology class, we read another paper, published in 2005, which was addressing the exact same question, in an almost identical way.  The difference is that they failed to make a transmissible virus.  If there is a concern about this kind of research, a concern that it is too risky to do these kinds of experiments, shouldn’t the alarm have been raised regardless of the outcome?  It just doesn’t make sense to me why it suddenly became so concerning.  If anything good has come of this controversy, it is the widespread discussion that this has stimulated on the importance of open communication of scientific data, the importance of not censoring in science.  Ironically, had we all been given access to the data, like through a journal publication, it would have been apparent that there wasn’t anything to be concerned about.


Evolving Avian Flu for Enhanced Transmission

Avian influenza (H5N1) infections have about 60% mortality rate. Only around 600 people are known to have been infected, so it is still a very rare but certainly deadly disease. Those infected are individuals who have direct contact with infected birds. Although some cases of human-to-human transmission have been suspected, good evidence for this is lacking. Its an important virus in agriculture too. When H5N1 is identified in domestic birds, the usual response is a massive cull, resulting in millions of birds killed and farmers left in great financial difficulty.

The question of whether such a virus could mutate to cause a human pandemic is an important one. In the history of flu pandemics, only H1, H2, or H3 viruses have been involved. Is it impossible for H5 to cause a pandemic, or has it simply not happened yet? If it could, would it retain the same level of pathogenicity, or in adapting to human-to-human transmission, would it become less virulent?

To answer the question of the possibility of human-to-human transmission, some researchers in the Netherlands performed some experiment to evolve H5N1 to become more transmissible. They infected ferrets, and over several passages (moving the virus from one animal to the next) managed to encourage transmission between ferrets. The virus adapted to transmission between ferrets, changing slightly from the original virus. The changes are minor, only 5 mutations in 2 genes. However, this research has caused some significant concern: they have generated a transmissible form of a highly pathogenic virus. Is this a good idea?

Importantly, the results have not been published so all this information is from news reports and interviews. Few people have seen the data.

This is what scientists call “dual-purpose” research. On the one hand, it can answer important questions. On the other, it can lead to the development of biological weapons, ideas for biological weapons, or seriously bad accidents. The best science writers are having a hard time not sensationalizing this. Even the researcher who did it seems to be playing up the drama. What if it gets out? Millions will die! But is there a real risk from this virus?

Its hard to know the facts without the published data.

How well does the ferret model the pathogenicity and transmissibility in humans? It is commonly used and generally accepted to be quite good, but it seems a stretch to assume a human pandemic can occur based on transmission between ferrets in the lab. We need to be careful not to over-extend the findings of the study (this is especially the case since the data is not available). The experiment presumably shows that the virus can be transmitted between ferrets. It does not demonstrate that this virus can cause a human pandemic.

How pathogenic is the new virus? Does it cause the same disease as the original virus or did the mutations that allow transmissibility also decrease virulence? Maybe it can spread human-to-human, but its not clear how sick they would get. Further, usually when a virus is passaged several times through a different host species, it adapts to that species and results in attenuation in the original host. This has been observed many times, and has even led to the development of several attenuated vaccines.

Related to this, many evolutionary biologists believe that virulence and transmission are closely tied. That is, a virus that is too deadly will cause outbreaks that fizzle out (Ebola is a good example). Viruses that don’t cause enough disease might have a hard time transmitting too (coughing, sneezing or diarrhea are good examples – a little bit of disease helps get the virus out of your bod and into the next one). Paul Ewald argued that the high mortality rate of the 1918 influenza was in part due to the fact that the conditions at the time allowed for a more deadly virus to evolve. Due to WWI, factors such as overcrowding and troop movements may have allowed a highly virulent virus to be successful. Conditions today may not favor a pandemic by a highly virulent virus. So would a transmissible and pathogenic H5N1 cause a major epidemic or would it fizzle out?

There is also the issue of publication. There is debate on whether the research should be published or kept secret. Does publication provide a roadmap for someone who wants to do this for evil purposes to repeat the experiment and create a biological weapon? It seems to me that even without details of the experiment, enough information is already available to repeat it. Withholding publication would also prevent other researchers from understanding and extending the findings. Any benefits from having done the experiments would be significantly less without publication.

I have seen stories like this one before. Several years ago, an highly pathogenic ectromelia virus (causes mousepox, related to the smallpox virus) was made by adding the gene for Interleukin-4. The researchers did not intend to make a highly pathogenic virus, it was rather a surprise to see this effect. There was much debate about whether they should publish, that perhaps this was a roadmap for building a highly pathogenic poxvirus in humans. They published and we have since learned more about the virus, including the observation that the virus does not transmit effectively, and that doing the same thing in other viruses doesn’t have the same effect. The more we know, the better.

I’d make the same argument here. I’d like to see the research published. The information from this study is probably valuable, addresses an important question, and is only one small step in understanding H5N1 influenza.


Taking control of the host to spread virus laden goo

Viruses are experts at hijacking cells to replicate, manipulating the conditions in the cell to optimize viral processes. But they manipulate their hosts on a higher level too, sometimes manipulating host behaviour to increase the chances of transmission. Take rabies virus for example: the virus induces aggression, then replicates abundantly in the salivary glands and stimulates salivation. The aggressive host is driven to bite, spreading the virus to its next host.

The basis for these bahavioural changes is poorly understood, on both the viral and host ends. However an experiment published in Science recently identifies the genetic basis for host behaviour manipulation by a baculovirus that infects the gypsy moth. When a baculovirus infects its host, the host eventually dies in a gruesome death appropriately called “virus melt.” The insect is liquefied, and the gooey, virus laden liquid drips down from the remains of the host on to the leaves below. Unsuspecting insects will then eat the contaminated leaves, becoming infected themselves.

So how could a virus maximize the dissemination of said liquid? How about having the host climb to the top of the plant and stay there to die, dripping all the liquid on the leaves below? The normal behaviour of the gypsy moth is to climb up a tree and munch on leaves during the night, and hide in crevices or climb down to the soil during the day, thus avoiding predation by birds. This behaviour is regulated by a hormone, 20-hydroxyecdysone, which tells the gypsy moth when to stop feeding and move down the tree (it also regulates molting and pupation). Baculovirus infected gypsy moths, however, climb up but don’t climb back down, staying up in the tree to die.

Baculoviruses expresses a gene that deactivates 20-hydroxyecdysone and prevents the infected host from leaving its “feeding state” and descending the tree. When researchers deleted the gene from the virus, the infected gypsy moths displayed normal behaviour.

I’d love to see a transmission experiment to see if the presence of this gene really helps with transmission to the next host.

(Also discussed on TWiV)


Variola virus evolution

Why do some people get severely ill with an infection while others catch the same virus but don’t get sick? There are many factors that can influence the progression and outcome of disease, but they can be lumped into four basic categories: host, agent, transmission and environment. For example, infection with Variola virus results in smallpox, but case fatality rates in different outbreaks range from very low to as high as 30%. Its likely that many factors contribute to this variability, but it’s likely that differences in viral strains is one of them.

Summers are quiet here at Vassar. There are no summer classes but we do have a program to support undergraduate research (“URSI”) so that students can gain some research experience and professors can get cheap labor. This summer I had a student working with me who is a Biochemistry major and Computer Science minor (called a “correlate” here). She can write code and I cant, so I had her working on a bioinformatics project. We were interested in investigating the difference between poxviruses that cause high mortality rates in humans (like some strains of Monkeypox virus and most strains of Variola virus) and those that dont. I recently published a paper along with another undergraduate student showing that certain genes in poxviruses are under Darwinian selective pressure. We wanted to test the hypothesis that the selective pressure differs between virulent and avirulent strains. She used several approaches involving analysis of synonymous and non-synonymous mutation rates to see if amino acid altering mutations were fixed at different rates in virulent and avirulent viruses.

As she crunched away at code writing and data analysis and discovered one of the joys(?) of science: failing to support your hypothesis. We could not find evidence that selective pressure differed between virulent and avirulent strains. Although no Vassar student wants to fail, failing to support a hypothesis is not actually failure. Rather, its an integral part of the scientific process, something that comes from the successful execution of an experiment that tests your hypothesis. The scientific method is actually quite humbling: you set up experiments that will tell you if you are wrong, and as a scientist, you have to get used to proving yourself wrong.

So now we must ask a new question: since some poxvirus genes show evidence of selective pressure, and that selection is not related to virulence, what is the cause of that pressure?


Swine Flu: New and Improved!

Contributed by guest blogger: Marni Hershbain ’11

Flu season is never enjoyable, but some seasons are certainly worse than others. The 2009 swine flu outbreak was particularly serious because the 2009 H1N1 strain was a novel virus, formed via the reassortment of swine, avian and human flu viruses. There were over 600,000 confirmed cases of H1N1 and over 18,449 deaths during the course of the pandemic. While this sounds pretty bad, it could have been much worse. The transmission efficiency of H1N1 was actually much lower than those of other pandemic strains, such as the 1918 H1N1 strain. Unfortunately, recent research demonstrates that this could change.

Flu strains are characterized by the hemagglutinin and neuraminidase found on their surfaces, hence names like H1N1. In order for the virus to infect a cell, hemagglutinin on the surface of the virus must bind to glycan receptors on the cell. Therefore, to explain the low transmission efficiency of 2009 H1N1, researchers looked to its hemagglutinin.
In most flu strains, the amino acids at positions 219 and 227 within the hemagglutinin are both hydrophobic or both charged. In 1918 H1N1 both are hydrophobic. However, the 2009 H1N1 strain has isolucine, a hydrophobic molecule, in position 219 and glutamic acid, a charged molecule, in position 227. Researchers hypothesized that lacking either hydrophobic or ionic interactions at these positions would disrupt the positioning of neighboring residues and decrease the hemagglutinin’s binding affinity. They further hypothesized that if they replaced isolucine with the charged amino acid lysine, stable inter-residue interactions would occur and binding affinity would increase.

When researchers compared the ability of wild type and isolucine→lysine mutant strains to bind to an array of glycans representing human binding sites, they found the binding ability of the mutant strain was 30 times greater. The mutant version also bound more intensely to receptors in human tracheal tissue. Researchers also infected ferrets (commonly used as models in human influenza studies) with either wild type or mutant virus. Only the ferrets infected with mutant virus spread the infection to all of the previously uninfected ferrets placed in close proximity to them.

The mutation of just one amino acid could greatly impact the transmission efficiency of 2009 H1N1. Flu viruses tend to mutate frequently, which is why a new vaccine needs to be developed every year. Predicting what these mutations will be is not an easy task, but mutations at the positions in this study will certainly be monitored closely.


The strangest family reunions

Contributed by guest blogger: Amelia McKitterick ’11

Next time you are sick from a viral infection, you should ask yourself if you’re just hosting a visit from distant relatives. Although “relative” might not seem like the most appropriate term for a virus, there has been evidence of a history viral influences and insertions into animal genomes, including that of humans!

A crucial step in the replication of RNA retroviruses is the integration of the viral genome into the host genome. Fragments of a viral genome in the genome of a non-viral cell are called endogenous viral elements (EVEs), and they can either be phased-out of the host genome or be passed on to become fixed within a population. A recent study examined genomes of a variety of mammals, birds, and insects for EVEs with matching amino acid sequences to extant, non RNA retroviruses. The genomes of 44 animals were converted into amino acid sequences and checked via tBLASTn (a BLAST that matches amino acid sequences with nucleotide sequences) for alignment with a library of currently known mammalian viruses with genomes larger than 100 kb in length. Matches were found to viruses with all types of RNA genomes (ss/ds, +/-, segmented, un-segmented) in all three of the major phyla tested, matches to DNA genomes (ss/ds, rt) were only found in mammals and birds, and even unclassifiable viral proteins were found in mammals that could represent extinct or undiscovered lineages.

But what is the use of all this new information? First, the data can be used to determine the minimum evolutionary divergence dates of different viral families based on host divergence dates. This study of paleovirology estimated the minimum ages of virus fossils Parvo-, Circo-, Filo- and Bornaviridae within the mammalian samples and found the oldest (Borna-) to be about 93 million years old, where it was originally infecting the distant relatives of the Afrotheria clade (Elephants, hyrax, tenrec, etc. For reference, the common ancestor of the primates evolved about 85 million years ago). A second use of the data is to illustrate the variety of viruses, and to give a better indication of the types of viruses that infect different hosts. The presence of the EVEs in a host genome can provide new insight about the replication process of non-reverse transcription viruses, and show patterns of host vulnerability. Similarly, new viruses, such as the unclassifiable EVE in mammals, could lead to new routes of investigation into the types of viruses and cures to infections.


Virus and Parasite Unite

Contributed by Guest Blogger: Joseph Zaino ‘11

Recent research has found a unique relationship between the intracellular parasite, Leishmania, and it’s corresponding Leishmania RNA virus-1 (LRV1). Ives et. al. concluded that Leishmania parasites, in the presences of LRV1, suppressed the host immune response and strengthened the pathogen’s persistence. Leishmania infects the human immune system by attacking macrophages. The parasite causes the infection known as leishmaniasis, which is typically transmitted by sand files. This is a serious infection, affecting an estimated 12 million people in the Mediterranean basin, Africa, the Middle East, Asia, Central and South America. The strain of parasite investigated by this study was mucocutaneous leishmaniasis (MCL). MCL destroys the soft tissues of the face and nasopharyngeal regions, as well as damages host immune responses.

Leishmania parasites are dependent on proinflammatory protein mediators called Toll-like receptors (TLRs). TLRs are found in intracellular vesicles of the macrophage- presumably the same vesicles that host Leishmania. Ives et. al. confirmed that TLR3-TRIF dependent pathways are essential for macrophage infection by Leishmania. The unusual part is that TLRs usually help the mammalian immune system to eliminate pathogens. Specifically, TLR-3 recognizes the double stranded RNA of many viruses that are released from dead parasites, unable to survive within their host. Observations found that between virally infected and non-virally infected Leishmania, the virally infected ones were more likely to successfully infect a host. Similarly, metastasizing parasites had greater levels of the LRVI virus than non-metastasizing parasites. The authors verified this finding by treating macrophages with purified LRVI, and observing the same phenotypic infection as the viral-infected Leishmania. Further models concluded that when TLR3 is deleted from macrophages, parasitic persistence was diminished.

This apparent mutualism seems to benefit both Leishmania and the virus by allowing a more successful rate of host infection. Many Leishmania species have lost RNAi interference pathways, allowing viruses to inhibit and replicate within them. In this case, the virally infected parasite is more persistent against macrophages, and more damaging to the mammalian immune system. Thus, it is advantageous for the parasite to coexist with the LRV1 virus. If severe MCL infections are contingent on LRV1 for infection, then future research can perhaps focus on this relationship in order to better understand and cure leishmaniasis.


Smelly Cucumbers Anyone?

Somewhat to my surprise, I have recently found myself very interested in plant viruses. This started a few years ago when I ate a most delicious variety of hot pepper that apparently is infected with a virus that gives the peppers white stripes. I’ve never really given much thought to plants and plant viruses before but as I began to look into their biology it seems that plant viruses have some terrific tricks up their sleeves (if you will) to aid in their transmission.
Plants aren’t walking around coughing on each other, so most of them depend on insects to come and bite the infected plant and carry the virus to the next host. But a plant that is infected isn’t very attractive to insects, since unhealthy plants aren’t as likely to be a valuable source of food. But viruses are masters of host manipulation. A recent study looked at Cucumber mosaic virus, and its ability to attract aphids to infected leaves. It seems that aphids dont like to spend much time on infected leaves, and they dont have to. The virus sticks to the aphid mouthparts quickly and easily and the aphid can then bring it to the next plant. But the aphids still have to be attracted to the leaves, even if they dont stay for long. So how does the virus attract the aphid to the plant? Researchers set up a special chamber with a leaf from an infected and a leaf from an uninfected plant. The leaves were not visible, but could be smelled by the aphids through wire mesh. Aphids released into the chamber were more attracted to the uninfected leaf. Analysis of volitile organic compounds being released from leaves showed that both infected and uninfected leaves release compounds that aphids can smell but infected leaves release much more. So even though the meal may not be as good, the strong smell brings the aphids to the table.