Tuesday, April 17, 2018

Back To The Bat Cave: More Influenza In Bats


Just over six years ago scientists from the U.S. CDC and the Universidad del Valle in Guatemala City announced the first discovery of an influenza virus from little yellow-shouldered bats (Sturnira lilium) captured at two locations in Guatemala (see A New Flu Comes Up To Bat).
This new influenza virus was described as deviating from the 16 known HAs and is designated as H17. The neuraminidase (NA), and internal genes, are also highly divergent from previously known influenzas.
In 2013 another new subtype (H18N11) was identified, again in South American Bats (see PLoS Pathogens: New World Bats Harbor Diverse Flu Strains), leading to speculation that these mammalian-adapted flu viruses might someday jump to other species – including man.

The CDC addressed the slim potential for these viruses posing a public health threat in their Bat Flu FAQ.

How could bat flu viruses become capable of infecting and spreading among humans?

Because the internal genes of bat flu viruses are compatible with human flu viruses, it is possible that these viruses could exchange genetic information with human flu viruses through a process called “reassortment.” Reassortment occurs when two or more flu viruses infect a single host cell, which allows the viruses to swap genetic information. Reassortment can sometimes lead to the emergence of new flu viruses capable of infecting humans.
However, the conditions needed for reassortment to occur between human flu viruses and bat flu viruses remain unknown. A different animal (such as pigs, horses, dogs or seals) would need to serve as a “bridge,” meaning that such an animal would need to be capable of being infected with both this new bat flu virus and human flu viruses for reassortment to occur.
Since the discovery of bat flu, at least one study has been conducted to assess the possibility of reassortment events occurring between bat flu and other flu viruses (3). So far, the results of these studies continue to indicate that bat flu viruses are very unlikely to reassort with other flu viruses to create new and potentially more infectious or dangerous viruses. In their current form bat flu viruses do not appear to pose a threat to human health.

Although unlikely, one plausible scenario would involve the reassortment of a bat and a mammalian virus in an intermediate host, such as a pig.

For the first few years only novel `bat specific' (H17 & H18) flu viruses were  detected in bats, suggesting a wide gap between human and bat flu.

Things became less certain in 2015 when PLoS One published Serological Evidence of Influenza A Viruses in Frugivorous Bats from Africa, which detected serological evidence of prior H9 influenza infection in roughly 30% of bats examined in Ghana.

The author's wrote:
Preliminary results indicate serological evidence against avian influenza subtype H9 in about 30% of the animals screened, with low-level cross-reactivity to phylogenetically closely related subtypes H8 and H12.
To our knowledge, this is the first report of serological evidence of influenza A viruses other than H17 and H18 in bats. As avian influenza subtype H9 is associated with human infections, the implications of our findings from a public health context remain to be investigated.

And while it isn't published in a peer-reviewed journal, a 2017 thesis by a student at the University of Airlangga, in Indonesia intriguingly suggests they've detected H3 in bats as well.  

Adding a bit of gravitas to these findings, Dr. Chairul Anwar Nidom, Prof. Dr., MS, DVM is listed as a contributor.  

Which brings us to a new study, published last week in the Virology Journal, that finds that bat receptor cells - while not ideally suited for human influenza viruses - appear somewhat better suited for avian flu viruses.

Only four influenza viruses were tested (see below), leaving open the possibility that other subtypes might produce decidedly different results.
  • Human H1N1 virus (A/USSR/77) (USSR H1N1)
  • Pandemic H1N1 2009 virus (A/California/07/2009) (pdm H1N1)
  • LPAI  H2N3 virus (A/mallard duck/England/7277/06)
  • LPAI H6N1 virus (A/turkey/England/198/09)
The full study is available, so follow the link to read it in its entirety.
Bat lung epithelial cells show greater host species-specific innate resistance than MDCK cells to human and avian influenza viruses

Tessa Slater, Isabella Eckerle and Kin-Chow Chang
Virology Journal201815:68

© The Author(s). 2018


With the recent discovery of novel H17N10 and H18N11 influenza viral RNA in bats and report on high frequency of avian H9 seroconversion in a species of free ranging bats, an important issue to address is the extent bats are susceptible to conventional avian and human influenza A viruses.


To this end, three bat species (Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis) of lung epithelial cells were separately infected with two avian and two human influenza viruses to determine their relative host innate immune resistance to infection.


All three species of bat cells were more resistant than positive control Madin-Darby canine kidney (MDCK) cells to all four influenza viruses. TB1-Lu cells lacked sialic acid α2,6-Gal receptors and were most resistant among the three bat species. Interestingly, avian viruses were relatively more replication permissive in all three bat species of cells than with the use of human viruses which suggest that bats could potentially play a role in the ecology of avian influenza viruses. Chemical inhibition of the JAK-STAT pathway in bat cells had no effect on virus production suggesting that type I interferon signalling is not a major factor in resisting influenza virus infection.


Although all three species of bat cells are relatively more resistant to influenza virus infection than control MDCK cells, they are more permissive to avian than human viruses which suggest that bats could have a contributory role in the ecology of avian influenza viruses.
While the results are far from a slam dunk, they do leave the door open to bats being a factor in the spread and evolution of avian flu viruses.
And as we discussed recently in Nature: Fatal Swine Acute Diarrhoea Syndrome Caused By An HKU2-related Coronavirus Of Bat Origin, bats are now known to play a much greater role in the harboring and transmission of zoonotic diseases than previously suspected.
In 2017 researchers from EcoHealth Alliance published a letter in Nature (Host and viral traits predict zoonotic spillover from mammals) providing the first comprehensive analysis of viruses known to infect mammals.

From their website summary:
The study shows that bats carry a significantly higher proportion of viruses able to infect people than any other group of mammals; and it identifies the species and geographic regions on the planet with the highest number of yet-to-be discovered, or ‘missing’, viruses likely to infect people. This work provides a new way to predict where and how we should work to identify and pre-empt the next potential viral pandemic before it emerges.
Which suggests that the more that we look into bats as reservoirs of dangerous pathogens, the more we are apt to find.

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