Bat-borne influenza A H9N2 virus shows species-specific replication and transmission
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Bat-borne H9N2 IAV (bat H9N2), initially detected in bat feces in Egypt in 2017, has recently attracted attention because of its unexpected pre-pandemic properties, including airborne transmission between ferrets and efficient replication in human lung explant cultures. However, its host range and potential reservoir hosts remain poorly defined, particularly with respect to additional bat hosts and mammalian or avian mixing-vessel species. Here, we compare the susceptibility of two pteropodid bat species, Rousettus aegyptiacus and Eidolon helvum , and additionally assessed pigs and quails following intranasal inoculation with bat H9N2.
Juvenile R. aegyptiacus showed only low-level viral replication and shedding, largely restricted to the upper respiratory tract, and did not show transmission to contact bats. In contrast, both juvenile and adult E. helvum , despite showing no clinical signs, showed high-level viral replication and shedding in the upper respiratory tract, with efficient and early transmission to contact bats. Viral RNA was most abundant in the respiratory turbinates, the nasopharyngeal meatus and the tracheal epithelium, where it was associated with moderate to severe necrotizing rhinitis and tracheitis. The lower respiratory tract was less involved, with viral RNA confined to scattered bronchioles and associated with focal necrotizing bronchiolitis. Other organs, including the gastrointestinal tract, lacked histologic lesions and viral RNA labeling. In pigs and quails, intranasal inoculation did not result in detectable replication, transmission, or seroconversion.
Our findings demonstrate marked differences in the susceptibility to bat H9N2 between the two fruit bat species tested and identify E. helvum as a highly susceptible host capable of rapid and efficient transmission. Conversely, pigs and quails were not susceptible, suggesting that additional viral adaptations may be required to allow for a productive infection in these species.
Author Summary
Bat-borne H9N2 IAV has raised concern because previous studies demonstrated efficient transmission between ferrets, replication in human lung tissue and human MxA-escape under experimental conditions [1]. This suggests that bat H9N2 has several characteristics associated with zoonotic potential. However, it remained unclear which bat species are susceptible to infection and capable of supporting virus transmission. Furthermore, it is unknown whether other mammalian species could serve as reassortment hosts for bat H9N2 with other IAVs.
Here, we experimentally tested the virus in two different Old World bat species, Eidolon (E.) helvum and Rousettus (R.) aegyptiacus , as well as in pigs and quails: R. aegyptiacus showed only low levels of bat H9N2 infection and did not transmit the virus to contact animals. In contrast, E. helvum supported high-level replication of bat H9N2 in the upper respiratory tract, also allowing efficient transmission to contact bats. Although subclinical, infection in this species was also associated with marked tissue damage in nose, throat, and trachea. In contrast, experimentally infected pigs and quails showed no evidence of viral replication, transmission, or immune responses. Our findings highlight that susceptibility to bat H9N2 is strongly species-dependent and identify E. helvum as a putative bat reservoir host.
