Epi Ren’s Journal Club: Bats and Flu, just what we needed

If you know me, then you’ll know that I’m a big geek when it comes to all things influenza. The virus is fascinating. It mutates often enough to stay ahead of our immune systems and ahead of the finest epidemiologists in the world. It has killed millions, and it can kill billions if the right circumstances arise. Influenza viruses can be found in all sorts of animals like birds, pigs, humans, and now… Bats.

So, yeah, in case you weren’t afraid of catching the flu because you think you’re invincible or something, now you have to fear this:


Fear the mammal!
[do action=”credit”]Photo credit: Furryscaly / Foter / CC BY-SA[/do]

A study, titled “New World Bats Harbor Diverse Influenza A Viruses“, published in PLOS, had scientists looking at the presence of influenza type A in bats. In case you don’t know, there are three types of influenza. Type A is the one that we see when we have pandemics. The reason for those pandemics is that type A can be carried around by pigs, birds and humans. This makes it easy for the virus to be around people and animals and have its genetic sequence re-assorted on a whim. That’s a bad thing because re-assortment of genes means new protein coat for the virus and less identification of it by our immune systems.

Type B influenza also gets you pretty sick, and it can even kill you. But it is only carried by humans and seals, so it can’t go around the world and re-assort as easily. It’s a little more stable in the genetic department. Type C influenza is even more stable and doesn’t cause widespread epidemics, though it can still make you sick.

Anyway, back to the study. The scientists looked for and identified a new type of influenza A virus in some bats in Peru. The virus is identified as H18N11. This means that the hemagglutinin protein on the virus surface is the 18th to be identified, while the neuraminidase is the 11th. Those Hs and Ns indicate the types of proteins on the surface of the virus. For example, the H1N1 that caused the recent pandemic had Hs and Ns similar to the ones first identified in the 1918 strain of influenza type A, hence the 1s. Hemagglutinin is the protein used by influenza viruses to attach to the respiratory cells of those they infect. The neuraminidase protein is used to break out of infected cells once thousands of copies of the virus is made. (Tamiflu, the antiviral medication used for influenza, is a neuraminidase inhibitor.)

Aside from discovering the virus, the scientists in this study noticed something interesting as well. From the abstract:

“Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells.”

Translation: The flu viruses carried by the bats are very genetically diverse. There’s lots of cousins. Lot’s or opportunity to infect and re-infect and evade the immune system over and over. Also, the neuraminidase and hemagglutinin in these viruses doesn’t matter to the bats. In short, the viruses are not infecting the bats and causing disease. The bats are carriers.

Why did they go looking for influenza in bats? Because bats have been known to carry other infectious diseases:

“Bats are a major source of emerging infectious diseases, including coronaviruses, filoviruses, henipaviruses, and lyssaviruses [3]–[5]. Their global distribution, abundance, diversity (~1200 species) and high population densities underscore the need to better understand the ecology and properties of influenza viruses that infect this mammalian order, as well as the potential of viral jumps across species barriers to emerge in new hosts [5]. These considerations prompted additional searches for species harboring novel influenza A viruses within the Americas, and detailed characterization of the virus-host interactions at the molecular and atomic levels.”

What did they do? They caught bats and swabbed their, uh, bottoms for the presence of influenza. In some bats that were positive for influenza, they did additional analyses to detect where the viruses were being kept. As it turns out, some had it in the gut, just like birds do, but not anywhere else, reinforcing the idea that the bats are carriers, mere vectors of these viruses and are not infected and made sick, like pigs and birds are:

“We sampled 114 Peruvian bats captured during 2010 in Truenococha and Santa Marta, two communities located in the Loreto Department, Peru, a remote and sparsely populated area in Amazonia… Initial screening of the available 110 rectal swabs with a pan Flu RT-PCR assay identified a flat-faced fruit bat (ID PEBT033) (Artibeus planirostris) from Truenococha as positive for influenza virus. Of the other available specimens, i.e. liver, intestine and spleen tissues from bat PEBT033, the intestine tissue specimen was strong positive whereas others were negative.”

Then they did phylogenetic analysis, which is a fancy way of comparing genes to see which viruses are related to which. It’s like making a family tree, or a map of relationships, between all the viruses. The results were surprising. There’s a lot of variance amongst the viruses, a lot of diversity.

“Considering the limited geographic area and bat species numbers sampled in the Americas, the remarkable divergence between A/bat/Peru/10 and Guatemalan bat viruses in these four gene segments suggests that New World bat species may carry a diverse pool of influenza viruses.”

In the discussion section, we are informed that these viruses have been with bats for a long time, and that these viruses are new to us, making it difficult to identify them by our standard lab methods should a human come down with a virus from these bats or a related virus that recombined with bats:

“Multiple lines of evidence suggest that influenza viruses have evolved in bats for an extended period of time: (i) in four of the eight gene segments, genetic diversity exceeds that observed in all other animal species combined; (ii) the divergence into multiple HA subtypes and utilization of alternative mechanisms for sialic acid-independent virion attachment to target cells and subsequent release; and (iii) the widespread geographic distribution in the Americas (Guatemala and Peru sampling sites are ~3,500 km apart) combined with a high seroprevalence in several bat species are indicative of an established infection, while the observation that the bat viruses form a monophyletic group is suggestive of sustained transmission in this species. The postulated ancient relationship of influenza viruses with aquatic migratory birds is consistent with the optimized parasitic relationship of the virus with ducks, involving subclinical infections with multiple virus subtypes as a result of efficient fecal-oral transmission. Although necessarily preliminary in nature, the data presented here suggest that similar ecological and evolutionary strategies may have been exploited by the influenza A viruses of New World bats.”

So what are the implications of this research? If it’s not clear to you yet, then let me explain some more about zoonoses. Zoonoses are infections acquired from animals. For example, cowpox is a zoonoses. Influenza caught from pigs, like the H1N1 that infected people in Mexico and then all over the world is a zoonoses. Rabies is also a zoonoses. Do you see where this is going? We need to know what is out there in nature so we can be aware of what will happen when the bats are driven out of their habitats by humans (or humans wander into their habitats). This research shows us that there are more influenza type A viruses out there than what we know, that they can be carried around by perfectly healthy bats that can fly long distances, and that the viruses can come together in a third species, e.g. a pig, and re-assort their genes, leading to all sorts of epidemiological fun.

If you’re interested in other infectious diseases coming to us from animals, I highly suggest the book “Spillover” by David Quammen. It will keep you up at night and make you wonder if it’s a good idea to keep deforesting the jungles or transporting wild species of animals across the globe for the fun of it.

[do action=”credit”]Featured image credit: Thomas Hawk / Foter / CC BY-NC[/do]

I'm a doctoral candidate in the Doctor of Public Health program at the Johns Hopkins University Bloomberg School of Public Health. All opinions posted here are my own, of course, and they do not necessarily reflect the opinions of my school, employers, friends, family, etc. Feel free to follow me on Twitter: @EpiRen

4 thoughts on “Epi Ren’s Journal Club: Bats and Flu, just what we needed

  1. While some may view the knowledge that bats are carriers of many known pathogens with alarm, I do not.
    For, I view it as an opportunity.
    An opportunity to “ask” the bat how they avoid infection and see if we can find a way to apply that to humans.*

    *By ask, I mean study thoroughly the mechanisms involved in permitting the bats to be only carriers and sickened by the virii they harbor.

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    • I like the way you think! Yes, we can learn a lot from natural progression of viruses and bacteria in the wild.

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  2. “Translation: The flu viruses carried by the bats are very genetically diverse. There’s lots of cousins.”

    And somewhere I heard that bats comprise the most diverse mammal species on this planet, which means that there are lots of different viruses that they encounter. I either read that in the book Spillover or heard on a This Week in Virology podcast.

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    • I’m not so sure about bats being the most diverse.
      Ignoring rodentia overall, mice alone are quite genetically diverse. Rats, not as much, but still quite diverse.
      Indeed, Mus has five subgenera, with different species within.
      If not a tie, it’s really close.

      Each carrying their own mixture of known pathogens, heaven knows how many unknown may lurk in the future.

      In my lifetime, first, the ocean floor was barren, indeed, sterile below 600 feet. Eventually, science actually *looked* and found it far from sterile, but quite populous. Indeed, life exists even at the greatest depths of ocean.
      Life didn’t exist below ground below a maximum of 100 feet. Then, life was found in the deepest diamond mine, the deepest mine on the planet.
      Radiation was lethal to *all* organisms. Then, microorganisms were found to be ignoring the radiation inside of the most heavily contaminated parts of the Chernobyl reactor.
      Bats were harmless, save for occasional cases of rabies.
      Now, bats are known to harbor a bewildering assortment of pathogens.

      Imagine what science will find next, when it decides to look at the humblest of sources.
      One only learns the truth when one actually looks.
      Then submits for peer review. 😉

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