Tag Archives: Ebola

Molecular Virology

Discovery of an Ebola-like virus in Spain

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Fans of Richard Preston’s The Hot Zone will know Ebola virus and Marburg virus as ones that causes their victims to die a horrific death, bleeding from every opening and turning organs into a bloody pulpy mess. Ebola outbreaks occur sporadically in central and west Africa, and despite extensive efforts, its still not known where the virus comes from. The best evidence is that bats carry the virus, and contact with bats or bat excrement in caves sparks the outbreaks. Ebola RNA has been detected in bats, but no one has been able to find live virus in bats.

But now a close relative of Ebola and Marburg viruses has been discovered in bats in Spain. And unlike Ebola and Marburg, which don’t cause disease in bats, it is possible that this newly identified virus is killing the bats. A recent bat die off in Spain killed several bat colonies in a little more than a week. So researchers searched for viral sequences in the bats and identified an new filovirus, and called it Lloviu virus, after the cave in which it was found. They found the same viral sequence in other caves that experienced die offs, and could not find evidence of the virus in healthy bats.

This finding is significant for several reasons. It is the first detection of a naturally occurring filovirus outside of Africa and The Philippines. The bats in Spain do not overlap with the known geographic range of Ebola and Marburg viruses so its unlikely that it would have been picked up there. There have been bat die offs across parts of western Europe, and it will be interesting to see if Lloviu virus is found at all these locations.

Also, it might be making the bats sick. The key word being might. In my class called “Microbial Wars” we have discussed Koch’s postulates and hopefully my students will recognize that these are far from fulfilled. Live virus has not yet been isolated from diseased animals, only detection of the viral genetic material. Researchers will need to demonstrate that experimental inoculation of bats with live Lloviu virus will cause the expected disease.

Cueva de Lloviu is frequented by tourists, so its possible that many people have been exposed to the virus without ever developing disease. So this is not a human health concern but it is an important discovery that may help us understand filoviruses better, especially with respect to their ecology.

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Guest Blogger

New Vaccine Protects Against Ebola Virus

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Contributed by Guest Blogger: S. Goldberg ’14

Ebola Virus (EBOV) is a fairly new infection of the Filoviridae family, that causes Ebola Hemorrhagic Fever, or EHF. This infection can often be severe or fatal in humans and primates. Because it would be difficult to create a vaccine against all four different virus species of Ebola, scientists came up with a plan to develop a vaccine protective against a single species of the infection. An experiment was designed to test to see if a “prime-boost” strategy would work, with a vaccine protecting against one Ebola Virus species and protecting a different species at the same time. In the process of doing this experiment, it was found that the vaccine developed to protect primates against the two most lethal Ebola Virus species also protected against the newer Ebola virus species that was founded in 2007. The prime-boost vaccination provides immunity against newly emerging EBOV species and shows cross-protection against EBOV infection. In this strategy, the “prime” is a DNA vaccine that has a small amount of genetic material with surface proteins of the Zaire Ebola virus species and the Sudan Ebola virus, the two most lethal species of EBOV. The “boost” is made of a weak cold virus that delivers the Zaire EBOV surface protein. The experiment, conducted and overseen by the National Institute of Allergy and Infectious Diseases and the US Army Medical, gathered eight 3 to 5 year old cynomolgus monkeys as their test subjects, to see if such a vaccine actually protected against the two older Ebola virus species and the newer strain. Each of the monkeys were given the immunization and then transferred to a laboratory where they were exposed to the EBOV infection. The monkeys stayed their for the duration of the experiment. Using a blood analyzer, liver enzyme levels were examined on “days 0, 3, 6, 10, 14, 21 and 32”. During this test, samples of T-cell intracellular cytokines were taken. CD8+ T-cells were stained with antibodies, against intracellular cytokines. This technique allows for the frequency of antigen-specific T-cells to be determined. The production of cytokines plays an important role in the immune response of the body. After isolating the RNA of each subject, each of the monkeys given a vaccine that contained Zaire EBOV and Sudan EBOV glycoprotein (GP). After the GP was exposed within each of the bodies, the subjects developed “robust antigen-specific…immune responses against the GP from [Zaire EBOV] as well as cellular immunity against lethal…[Bundibugyo EBOV]”. After concluding this experiment, scientists have learned that current vaccines that can bring about T-cell immunity will have a greater possibility of “protecting against other [new] pathogenic EBOV species”.
If we have the ability to protect against new and emerging EBOV species, does that mean that, in the long-run, mutation of the virus will stop? Will existence of any EBOV species disappear? If it disappears, could it reappear? Could similar experiments be done to discover if a other currently used vaccines, aside those that display T-cell immune responses, are protecting against other unknown or new viral strains?

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Guest Blogger

A new host for Ebola

Contributed by Guest Blogger: S. Brucker ’14

Ebolavirus is a relatively new threat to the living world and therefore still enigmatic to the medical community in many ways. The question of where Ebolavirus strains come from remains unsettled, but they are thought to mainly infect humans and non-human primates. However, the feasible targets for Ebola expanded when researchers ran tests on pigs in the Philippines. A recent porcine epidemic in the Philippines lead the worried government to contact the USDA along with other mammalian medical laboratories for help diagnosing the problem. The disease was originally thought to solely be Porcine Respiratory and Reproductive Syndrome Virus (PRRSV) also known as “Blue Ear Disease,” but as it turns out, the swine were carrying something else. A technique called microarray analysis was used to identify any other pathogens infecting the pigs. This process consists of comparing an unknown genetic sample to an array of signature sequences belonging to known pathogens. The results of this test showed 28 out of 28 positive matches of the pigs’ genetic samples to signature Reston Ebolavirus (REBOV) sequences. This finding came as a surprise to a scientific community who believed Ebola to only infect primates. This seemingly small discovery has large implications for the way we think abut Ebola. Although Reston Ebolavirus has not yet been shown to infect humans, it is of concern that Ebola strains are appearing in the human food chain. This discovery leads to many questions that must be answered. How long has Ebola been able to infect pigs? If it recently evolved to include pigs in its host tropism, then what is different about this strain? What else can it affect? Are more virulent strains also going to evolve to expand host range? The biggest danger about Ebola is the fact that there is so much that we do not know about it, and until we answer these questions, the virus will be a constant threat.
 

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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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