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.
I know you were thinking the same thing! Bats are suspected reservoirs for several zoonotic viruses that can cause significant disease in humans or other animals. These include the dreaded Ebola virus, Nipah virus (which causes outbreaks of encephalitis in South East Asia), Hendravirus (which causes disease in horses) and several others. So knowing what viruses are carried by bats will be important in understanding emerging zoonoses.
Several studies have identified a diverse array of viruses in bats, but using next-generation sequencing it is now possible to investigate the population of viruses carried in bats to a much deeper level. In a study published last summer, guano from bats in California and Texas was collected by placing plastic sheets below the bat roosts. The individual roosts were occupied by as many as four different bat species, so the guano collected was a mix from the different inhabitants. To isolate viral DNA and RNA, the samples were filtered to remove cells then treated with nucleases to destroy any free DNA or RNA, leaving only encapsidated viral genetic material.
In the sequenced “virome” or population of viruses in the samples, only 51-39% of the sequences(depending on collection site) had matches to genbank sequences. So once again, viromic sequencing shows us how little we know about the viral world. Of those sequences that matched known sequences, most were insect and plant viruses. The bats are insectivores and the insects are herbivores, so you can see the viral populations from each link in the food chain. Only a very small proportion of the virome was of bacteriophage origin, much less than other viromic studies in humans and horses, although its not clear why there would be such a difference. Among mammalian viruses, which made up less thatn 10% of the sequences, there were adenoviruses, coronaviruses, parvoviruses, circoviruses, astrovirsues, picornaviruses and even poxviruses. Most of these sequences only matched less than 60% to known mammalian viruses however, so its unlikely that they pose a zoonotic threat.
As researchers continue to sequence viral populations, we keep seeing mostly novel sequences, something that has decreased in bacterial and eukaryotic sequencing. That tells us we have a lot more sequencing to do if we want to understand global viral diversity. In bats however, the major question is not so much about the diversity but the threat of zoonoses. It will be interesting to see the guanome of bats in areas where zoonoses are a real problem, and I wonder if this will be a technique useful to monitor the threat of emergent diseases as the cost of high throughput sequencing continues to drop.
Contributed by Guest Blogger: D. Patel ’14
Deadly human diseases including HIV Aids, swine flu and rabies are infectious diseases where the viruses have jumped from one animal species into another and now infect humans too. This is a phenomenon known as cross-species transmission (CST). Understanding this process is the key to predicting and preventing future outbreaks.
The scientists who researched CST and wrote this paper made a groundbreaking discovery into how viruses jump from host to host. They used and thought of rabies as an ideal system because it occurs across the country, affects many different host species, and is known to mutate frequently. Although cases of rabies in humans are rare in the U.S., bats are a common source of infection. Hence, the study was based on and narrowed down to CST events among different bat species.
To determine the rate of CST, a large dataset containing hundreds of rabies viruses from 23 North American bat species was used. Population genetics tools were used to quantify how many CST events were expected to occur from any infected individual and the cases were verified by genotyping both the viruses and the bats.
The study showed that depending on the species involved, a single infected bat may infect between 0 and 1.9 members of a different species; and that, on average, CST occurs only once for every 72.8 transmissions within the same species. This means that the majority of viruses from cross-species infections were tightly nested among genetically similar bat species.
It is a long-held belief that CST depends on virus mutation and contact of the host with other species. However, this study showed that CST may have more to do with host similarity. The similarity in the defenses of closely related species may favor virus exchange by making it easier for natural selection to favor a virus’ ability to infect new hosts.
Whether other factors (like evolution of viruses) are enough to overcome the genetic differences between hosts remains questionable. However, the basic knowledge gained through the study is key to developing new intervention strategies for diseases that can jump from wildlife to humans.