J. Virology: Isolation & Characterization of a Distinct Influenza A virus from Egyptian Bats

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In 2012 scientists from the U.S. CDC and the Universidad del Valle in Guatemala City announced the first discovery of an influenza A 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 was designated as H17. The neuraminidase (NA), and internal genes, were 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). The CDC addresses 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.

But in 2015 PLoS One published Serological Evidence of Influenza A Viruses in Frugivorous Bats from Africa, which detected serological evidence of prior H9 influenza infection - a subtype which has infected humans - 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. 

Just last April we looked at a study published 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 (see Bat lung epithelial cells show greater host species-specific innate resistance than MDCK cells to human and avian influenza viruses).

All of which brings us to a new study, published in the Journal of Virology, that describes the isolation and characterization of a genetically distinct Influenza A H9-like virus from Egyptian fruit bats which already demonstrate the ability to replicate in the lungs of experimentally infected mice.

The full article is behind a pay wall, but we have the following abstract available. After the break, I'll return with a bit more on our growing understanding of the remarkable host range of influenza (A,B,C & D) viruses.

Isolation and characterization of a distinct influenza A virus from Egyptian bats 

Ahmed Kandeil, Mokhtar R. Gomaa, Mahmoud M. Shehata, Ahmed N. El Taweel, Sara H. Mahmoud, Ola Bagato, Yassmin Moatasim, Omnia Kutkat, Ahmed S. Kayed, Patrick Dawson, Xueting Qiu, Justin Bahl, Richard J. Webby, William B. Karesh, Ghazi Kayali, Mohamed A. Ali
DOI: 10.1128/JVI.01059-18

ABSTRACT
Recently, two genetically distinct influenza viruses were detected in bats in Guatemala and Peru. We conducted influenza A surveillance among four bat species in Egypt. Out of 1202 swabs, 105 were positive by RT-PCR. A virus was successfully isolated in eggs and propagated in MDCK cells in the presence of TPCK-treated trypsin. 

Genomic analysis revealed that the virus was phylogenetically distinct from all other influenza A viruses. Analysis of the HA gene suggested common ancestry with other H9 viruses and the virus showed low-level of cross-reactivity with sera raised against H9N2 viruses. Bats were seropositive for the isolated viruses. The virus replicated in the lungs of experimentally infected mice. While genetically distinct, this virus shares several avian influenza virus characteristics suggesting a more recent avian host origin.

 IMPORTANCE 

Through surveillance, we isolated and characterized an influenza A virus from Egyptian fruit bats. This virus had affinity to avian-like receptors but was also able to infect mice. Our findings indicate that bats may harbor a diversity of influenza A viruses. Such viruses may have the potential to cross the species barrier to infect other species including domestic birds and mammals and possibly humans.

        (Continue . . . )


Another previously unknown influenza virus type came to light in 2013, when researchers reported finding a novel influenza virus in swine from Oklahoma - initially classified as a novel Influenza C virus - but which would later be designated as Influenza D. 

Their research – published PLoS Pathogens – was called Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses, and it immediately caused a stir in the flu research community.

The authors found that this new (provisional) influenza C virus could infect, and transmit, in both ferrets and pigs. The following year, in mBio: Characterizing A Novel Influenza C Virus In Bovines & Swine, cattle were added to the list, and appeared to be the virus's primary reservoir. 

And while it isn't known if Influenza D viruses (IDVs) can cause symptomatic illness in humans, in 2016, in Serological Evidence Of Influenza D Among Persons With & Without Cattle Exposure, researchers reported finding a high prevalence of antibodies against Influenza D among people with cattle exposure.  They wrote:

IDV poses a zoonotic risk to cattle-exposed workers, based on detection of high seroprevalence (94–97%). Whereas it is still unknown whether IDV causes disease in humans, our studies indicate that the virus may be an emerging pathogen among cattle-workers.

Last August, Veterinary Sciences published an excellent review of these recently discovered flu viruses in bats and in cattle.

Novel Flu Viruses in Bats and Cattle: “Pushing the Envelope” of Influenza Infection

Suresh V. Kuchipudi* and Ruth H. Nissly

While the entire open-access article is well worth reading, I've excerpted one particular graphic showing the known host reservoirs for influenza A, B, C & D Viruses.

Of particular note, only 4 species - humans, horses, pigs, and seals - are known to be infected by more than one influenza type (A, B, C or D), and of those only 2 - humans and pigs - are believed susceptible to all four. 

Influenza A remains the only influenza virus type with a history of sparking human pandemics, but very little is known about influenza pandemics prior to the year 1900, making our frame of reference barely over 100 years.

While the greatest influenza threat to mankind are currently human, swine, and avian influenza A viruses, the Vet. Sci. article concludes with these cautionary notes:

Influenza A, B, C and D viruses have varying susceptible host range (Figure 1). Notably, the newly discovered IDVs have the widest host range after IAVs. Further, humans and pigs are susceptible to infection by all four types of influenza viruses.

With the extensive host range that continues to grow and the zoonotic potential, influenza viruses remain a major challenge to epidemiologists. Owing to their tremendous potential to affect animal and human health, there is a need to carry out in-depth and comprehensive studies to unravel the ecological complexity of influenza virus host range evolution.

In particular, we feel that researchers should focus on answering the key questions, “what is the role of bats in the ecology and evolution of IAVs?”, “are IDVs involved in the epidemic influenza infections in people?”, and “are birds susceptible to infection by IDVs?”

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A reminder that the deeper we look, the more we find.