Wednesday, November 12, 2025

Preprint: Spillover of H5 Influenza Viruses to Vampire Bats at the Marine-terrestrial Interface

Credit Wikipedia


#18,942

One of the threats we've discussed repeatedly over the past few years has been the potential ramifications when a formerly geographically and host restricted virus - like HPAI H5Nx - begins to 1) spread globally2) spill over into new hosts, and 3) reassorts with new viruses. 

After 2 decades of being primarily an Asian, Middle Eastern, and occasionally European problem - H5N1 (over the past 4 years) has become endemic in the Western Hemisphere, and now has its sights set on Oceania (Australia/NZ). 

After its arrival in North America in late 2021, we saw the sudden (and continual) generation of scores of new genotypes, and the spillover into many new avian and mammalian species. For the first time, dairy cattle - and other non-poultry livestock - were at risk, along with domestic cats and other peridomestic animals

After HPAI H5N1 found its way into South America, it quickly became endemic in marine mammals, killing tens of thousands of animals from Peru to Argentina (see Nature Comms: Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b HPAI A/H5N1 with PB2 adaptations).

In both instances, exposure to new, immunologically naive hosts - and reassortment with locally circulating LPAI viruses - resulted in the explosive spread, and rapid evolution, of the HPAI virus. 
With HPAI now seemingly poised to invade Australia/NZ - which boasts some of the most unique (and isolated) fauna in the world - one can't help but wonder what unexpected impacts that might have on its future course and trajectory.

All of which brings us to a preprint which - while sounding like a premise for a cheesy made-for-cable Sci Fi movie - actually illustrates another example of the unexpected consequences of HPAI's globe-trotting, and promiscuous, ways. 

But first, a brief side excursion into the brief history influenza A in bats. 

  • Which was unknown until 2012, when a new H17 virus (see A New Flu Comes Up To Bat) was discovered in little yellow-shouldered bats (Sturnira lilium) captured at two locations in Guatemala.
For the next couple of years only novel `bat specific' (H17 & H18) flu subtypes were detected in bats, suggesting a wide gulf between human and bat flu. 
But in 2015 PLoS One published Serological Evidence of Influenza A Viruses in Frugivorous Bats from Africa - which described serological evidence of prior H9 influenza infection in bats tested in Ghana - raising new questions about the range of flu viruses carried by bats. 
In 2018 (see J. Virology: Isolation & Characterization of a Distinct Influenza A virus from Egyptian Bats) a study described the isolation and characterization of a genetically distinct Influenza A H9-like virus from Egyptian fruit bats which already had the ability to replicate in the lungs of experimentally infected mice.

In 2023, in Preprint: The Bat-borne Influenza A Virus H9N2 Exhibits a Set of Unexpected Pre-pandemic Features, we learned that Egyptian H9N2 virus already ticked a lot of the pre-pandemic boxes;
    • it readily infects and transmits incredibly well among ferrets
    • it replicates efficiently in human (explant) lung tissue
    • is able to escape human MxA (myxovirus resistance protein A)
    • there appears to be little pre-existing community immunity to H9 viruses 
Suddenly, the idea that bats could carry human-susceptible influenza A viruses wasn't quite so outlandish. 
Which brings us to today's preprint, which finds serological evidence of HPAI H5 infection in coastal vampire bats (Desmodus rotundus) in Peru, a region where marine mammals have been particularly hard hit by the avian flu virus.

At this point, there is no evidence of sustained transmission among bats, and no live virus was isolated from these samples. But this is the first evidence of HPAI H5 infection in bats, and it suggests that HPAI may have found yet another unconventional avenue by which to spread and/or evolve. 

I've posted the Abstract, and a brief excerpt. Follow the link to read it in its entirety.  I'll have a postscript after the break. 

Spillover of H5 influenza viruses to vampire bats at the marine-terrestrial interface
I-Ting Tu, Christina Lynggaard, Lorin Adams, Sarah K Walsh, Hanting Chen, Savitha Raveendran, Matthew L Turnbull, Megan E Griffiths, Rita Ribeiro, Jocelyn G Perez, William Valderrama Bazan, Carlos Tello, Carlos Zariquiey, Kristhie Pillaca Rodriguez, Marco Risco, Illariy Quintero Mamani, Wendi Chavez, Roselvira Zuniga Villafuerte, Joaquin Clavijo Manuttupa, Jean Pierre Castro Namuche, Andres Moreira-Soto, Jan Felix Drexler, Gustavo Delhon, Christina Faust,Susana Cardenas-Alayza, Ed Hutchinson, Pablo R Murcia, Massimo Palmarini, VKristine Bohmann,Ruth Harvey, Daniel G Streicker
doi: https://doi.org/10.1101/2025.11.09.686930
This article is a preprint and has not been certified by peer review [what does this mean?].

Preview PDF

Abstract

The highly pathogenic H5N1 avian influenza A virus (IAV) clade 2.3.4.4b has spread globally and spilled over into multiple mammalian species, raising concerns about its pandemic potential. In late 2022, clade 2.3.4.4b viruses devastated seabird and marine mammal populations along the Pacific coast of South America. 

Here, we report the first evidence of H5 IAV infections in wild bats globally, focusing on common vampire bats (Desmodus rotundus) in coastal areas of Peru. Longitudinal serological screening, stable isotope analysis and metabarcoding revealed repeated exposures to H5 IAVs in vampire bats which feed on coastal wildlife species heavily impacted by the 2.3.4.4b epizootic, but no evidence of infection in populations without access to marine prey. 

We further report bat gene flow between IAV-exposed and IAV-naive populations, and IAV infections in a vampire bat colony that fed on both marine and terrestrial livestock prey, providing insights into how future IAV epizootics might spread spatially within bats and between marine and terrestrial ecosystems if a bat reservoir were established. 

Immunohistochemistry demonstrated that the H5 haemagglutinin protein binds to the upper respiratory tract of vampire bats, suggesting bat tissue susceptibility to H5 IAVs. Finally, vampire bat-derived kidney, liver, and lung cells supported entry, replication, and egress of avian and mammalian 2.3.4.4b viruses, confirming cellular infectivity

These results illustrate how combining ecological inference and experimental virology can pinpoint the species origins and biological significance of viral spillover at species interfaces.
Recurrent exposures from marine wildlife, tissue and cellular susceptibility to H5N1 IAVs, and connections to other IAV-susceptible terrestrial mammals establish the prerequisite conditions for vampire bats to spread IAVs between marine and terrestrial environments or to form a novel reservoir of highly pathogenic IAVs.

       (SNIP)

Understanding virus spillover at species interfaces is of paramount importance to pandemic preparedness. Yet, because spillover is shaped by inter-specific interactions that create opportunities for exposure and by host physiological barriers which determine whether exposures lead to infection, assessing spillover risk has been notoriously challenging - requiring multidisciplinary efforts to unify ecological and virological processes32.
By integrating field surveillance, molecular and chemical ecology, tissue analyses and virological assays, were construct the exposure routes of a potential novel bat host to IAV-affected species, identify onward transmission pathways through high-resolution mapping of species interactions, and experimentally rule out hard physiological barriers to infection.
While our current data support limited H5 IAV transmission among bats, the recurrent nature of spillover events, ongoing mammalian adaptation, and prospects for reassortment with other mammalian IAVs, indicate that bats may constitute an open door for future IAV emergence which require closer investigation.

        (Continue . . . )

 

While HPAI H5 infected vampire bats are unlikely to present a direct public health threat any time soon, they could play a role in the cross-species transmission of the virus (e.g., from marine mammals to livestock) in some regions of South America. 

They could also potentially serve as a `mixing vessel' between HPAI and other novel flu viruses, either now or in the future. 

Much of the spread, transmission, and evolution of HPAI H5 (and other novel viruses) occurs outside of our view. The USDA's Detections of Highly Pathogenic Avian Influenza in Mammals (see below), has seen a dramatic drop in reports from states over the past year, despite high levels of the virus reported across the nation's wild birds, cattle, and poultry. 


Some states have yet to report a single instance, while other have reported dozens.  But even from the states that do report, we get disappointingly few details.  
Our willingness to `look the other way' when it comes to HPAI may pay economic or political dividends in the short term, but if HPAI H5 ever gets `lucky', it could quickly become too big to ignore.  
At which point we'll regret every day we squandered hoping it would go away.