Bat Influenza Research Articles

Incompatible packaging signals and impaired protein functions hinder reassortment of bat H17N10 or H18N11 segment 7 with human H1N1 influenza A viruses.

Reassortment is one of the mechanisms in fast evolution of influenza A viruses (IAVs) and responsible for generating pandemic strains. To date, why novel bat IAVs are incapable of reassorting with conventional IAVs remains completely understood. Here, we attempted to rescue recombinant PR8 viruses with M segment from bat IAVs to understand the molecular mechanisms in hindering their reassortment. Results showed that bat influenza NEP and M1 have similar functions as respective counterparts of PR8 to medicating viral ribonucleoprotein nuclear export. Moreover, the incompatible packaging signals of M genes from bat and conventional IAVs and impaired bat M2 functions are the major reasons to hinder their reassortment. Recombinant PR8 viruses with bat influenza M open reading frames were generated but showed attenuation, which correlated with the functions of the bat M2 protein. Our studies provide novel insights into the molecular mechanisms that restrict reassortment between bat and conventional IAVs.

Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level.

Jamaican fruit bats (Artibeus jamaicensis) naturally harbor a wide range of viruses of human relevance. These infections are typically mild in bats, suggesting unique features of their immune system. To better understand the immune response to viral infections in bats, we infected male Jamaican fruit bats with the bat-derived influenza A virus (IAV) H18N11. Using comparative single-cell RNA sequencing, we generated single-cell atlases of the Jamaican fruit bat intestine and mesentery. Gene expression profiling showed that H18N11 infection resulted in a moderate induction of interferon-stimulated genes and transcriptional activation of immune cells. H18N11 infection was predominant in various leukocytes, including macrophages, B cells, and NK/T cells. Confirming these findings, human leukocytes, particularly macrophages, were also susceptible to H18N11, highlighting the zoonotic potential of this bat-derived IAV. Our study provides insight into a natural virus-host relationship and thus serves as a fundamental resource for future in-depth characterization of bat immunology.

Cross-species spill-over potential of the H9N2 bat influenza A virus

In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2). The virus has a pH inactivation profile and neuraminidase activity similar to those of human-adapted IAVs. Despite the virus having an avian virus–like preference for α2,3 sialic acid receptors, it is unable to replicate in male mallard ducks; however, it readily infects ex-vivo human respiratory cell cultures and replicates in the lungs of female mice. A/bat/Egypt/381OP/2017 replicates in the upper respiratory tract of experimentally-infected male ferrets featuring direct-contact and airborne transmission. These data suggest that the bat A(H9N2) virus has features associated with increased risk to humans without a shift to a preference for α2,6 sialic acid receptors.

Has avian influenza virus H9 originated from a bat source?

Influenza A viruses are important pathogens that can cause diseases with high mortality in humans, animals, and birds; and wild birds are considered the primary reservoir of all subtypes in nature. After discovering the H9 influenza A viruses in bats, questions arose about their potential to serve as an additional natural reservoir and about the priority of the viral origin: Did the virus initially circulate in bats and then transmit to birds or vice versa? Influenza A viruses of the H9 subtype are of particular interest because fatal infections of humans caused by H5, H7, and H10 influenza viruses contained RNA segments from H9 viruses. Recently, a novel subtype of influenza A virus (H19) was reported and it was closely related to the H9 bat influenza A virus by its hemagglutinin structure. The genome of novel H19 has revealed a mixed characteristic genomic signature of both avian and bat influenza viruses. The time to most recent common ancestor (TMRCA) estimates have shown that the divergence time between the bat and avian H9-similar influenza virus occurred approximately at the end of the XVIII century. This article discusses the evolution and possible origin of influenza viruses of the H9 subtype isolated from bats and birds. The obtained data, along with the known data, suggest that the primary reservoir of the H9 influenza virus is wild birds, from which the virus was transmitted to bats. We hypothesize that the novel H19 could be a descendant of an intermediate influenza virus that was in the transition stage of spillover from avian to bat hosts.

The M2 proteins of bat influenza A viruses reveal atypical features compared to conventional M2 proteins.

The influenza A virus (IAV) M2 protein has proton channel activity, which plays a role in virus uncoating and may help to preserve the metastable conformation of the IAV hemagglutinin (HA). In contrast to the highly conserved M2 proteins of conventional IAV, the primary sequences of bat IAV H17N10 and H18N11 M2 proteins show remarkable divergence, suggesting that these proteins may differ in their biological function. We, therefore, assessed the proton channel activity of bat IAV M2 proteins and investigated its role in virus replication. Here, we show that the M2 proteins of bat IAV did not fully protect acid-sensitive HA of classical IAV from low pH-induced conformational change, indicating low proton channel activity. Interestingly, the N31S substitution not only rendered bat IAV M2 proteins sensitive to inhibition by amantadine but also preserved the metastable conformation of acid-sensitive HA to a greater extent. In contrast, the acid-stable HA of H18N11 did not rely on such support by M2 protein. When mutant M2(N31S) protein was expressed in the context of chimeric H18N11/H5N1(6:2) encoding HA and NA of avian IAV H5N1, amantadine significantly inhibited virus entry, suggesting that ion channel activity supported virus uncoating. Finally, the cytoplasmic domain of the H18N11 M2 protein mediated rapid internalization of the protein from the plasma membrane leading to low-level expression at the cell surface. However, cell surface levels of H18N11 M2 protein were significantly enhanced in cells infected with the chimeric H18N11/H5N1(6:2) virus. The potential role of the N1 sialidase in arresting M2 internalization is discussed. IMPORTANCE Bat IAV M2 proteins not only differ from the homologous proteins of classical IAV by their divergent primary sequence but are also unable to preserve the metastable conformation of acid-sensitive HA, indicating low proton channel activity. This unusual feature may help to avoid M2-mediated cytotoxic effects and inflammation in bats infected with H17N10 or H18N11. Unlike classical M2 proteins, bat IAV M2 proteins with the N31S substitution mediated increased protection of HA from acid-induced conformational change. This remarkable gain of function may help to understand how single point mutations can modulate proton channel activity. In addition, the cytoplasmic domain was found to be responsible for the low cell surface expression level of bat IAV M2 proteins. Given that the M2 cytoplasmic domain of conventional IAV is well known to participate in virus assembly at the plasma membrane, this atypical feature might have consequences for bat IAV budding and egress.

Evolutionarily conserved amino acids in MHC-II mediate bat influenza A virus entry into human cells

The viral hemagglutinins of conventional influenza A viruses (IAVs) bind to sialylated glycans on host cell surfaces for attachment and subsequent infection. In contrast, hemagglutinins of bat-derived IAVs target major histocompatibility complex class II (MHC-II) for cell entry. MHC-II proteins from various vertebrate species can facilitate infection with the bat IAV H18N11. Yet, it has been difficult to biochemically determine the H18:MHC-II binding. Here, we followed a different approach and generated MHC-II chimeras from the human leukocyte antigen DR (HLA-DR), which supports H18-mediated entry, and the nonclassical MHC-II molecule HLA-DM, which does not. In this context, viral entry was supported only by a chimera containing the HLA-DR α1, α2, and β1 domains. Subsequent modeling of the H18:HLA-DR interaction identified the α2 domain as central for this interaction. Further mutational analyses revealed highly conserved amino acids within loop 4 (N149) and β-sheet 6 (V190) of the α2 domain as critical for virus entry. This suggests that conserved residues in the α1, α2, and β1 domains of MHC-II mediate H18-binding and virus propagation. The conservation of MHC-II amino acids, which are critical for H18N11 binding, may explain the broad species specificity of this virus.

Development of accelerated high-throughput antiviral screening systems for emerging orthomyxoviruses

Bourbon virus (BRBV) is an emerging tick-borne orthomyxovirus that causes severe febrile illness in humans. There are no specific treatments for BRBV disease currently available. Here, we developed a highly accessible and robust, quantitative fluorescence-based BRBV minigenome (MG) system and applied it to high-throughput antiviral drug screening. We demonstrated that human dihydroorotate dehydrogenase (DHODH) inhibitors, hDHODH–IN–4 and brequinar, efficiently reduced BRBV RNA synthesis, and validated these findings using infectious BRBV in vitro. The DHODH inhibitors also exhibited high potency in inhibiting MG activities of other orthomyxoviruses with emerging zoonotic potential, including bat influenza A virus, swine influenza D virus, and Thogoto virus. Our newly developed MG system is a powerful platform for antiviral drug screening across the Orthomyxoviridae family, enabling rapid development and deployment of antivirals against future emerging orthomyxoviruses.

Different but Not Unique: Deciphering the Immunity of the Jamaican Fruit Bat by Studying Its Viriome.

A specialized and fine-tuned immune response of bats upon infection with viruses is believed to provide the basis for a “friendly” coexistence with these pathogens, which are often lethal for humans and other mammals. First insights into the immunity of bats suggest that bats have evolved to possess their own strategies to cope with viral infections. Yet, the molecular details for this innocuous coexistence remain poorly described and bat infection models are the key to unveiling these secrets. In Jamaican fruit bats (Artibeus jamaicensis), a New World bat species, infection experiments with its (putative) natural viral pathogens Tacaribe virus (TCRV), rabies virus (RABV), and the bat influenza A virus (IAV) H18N11, have contributed to an accurate, though still incomplete, representation of the bat-imposed immunity. Surprisingly, though many aspects of their innate and adaptive immune responses differ from that of the human immune response, such as a contraction of the IFN locus and reduction in the number of immunoglobulin subclasses, variations could also be observed between Jamaican fruit bats and other bat species.

The Species-Specific 282 Residue in the PB2 Subunit of the Polymerase Regulates RNA Synthesis and Replication of Influenza A Viruses Infecting Bat and Nonbat Hosts.

Bat influenza viruses are genetically distant from classical influenza A viruses (IAVs) and show distinct functional differences in their surface antigens. Nevertheless, any comparative analyses between bat and classical IAV RNA polymerases or their specific subunits are yet to be performed. In this work, we have identified signature residues present in the bat influenza virus polymerase which are responsible for its altered fitness in comparison to the classical IAVs. Through comparative sequence and structural analysis, we have identified specific positions in the PB2 subunit of the polymerase, with differential amino acid preferences among bat and nonbat IAVs. Functional screening helped us to focus upon the previously uncharacterized PB2-282 residue, which is serine in bat virus but harbors highly conserved glutamic acid in classical IAVs. Introduction of E282S mutation in the human-adapted PB2 (influenza A/H1N1/WSN/1933) drastically reduces polymerase activity and replication efficiency of the virus in human, bat, and canine cells. Interestingly, this newly identified PB2-282 residue within an evolutionary conserved "S-E-S" motif, present across different genera of influenza viruses and serving as a key regulator of RNA synthesis activity of the polymerase. In contrast, bat influenza viruses harbor an atypical "S-S-T" motif at the same position of PB2, alteration of which with the human-like "S-E-T" motif significantly enhances its (H17N10/Guatemala/164/2009) polymerase activity in human cells. Together, our data indicate that the PB2-S282 residue may serve as an inherent restriction element of the bat virus polymerase, limiting its activity in other host species. IMPORTANCE Influenza A viruses are known for their ability to perform cross-species transmission, facilitated by amino acid alterations either in the surface antigen hemagglutinin (HA) or in the polymerase subunit PB2. Recent isolation of influenza A-like viruses from bats raised concern about their epizootic and zoonotic potential. Here, we identify a novel species-specific signature present within the influenza virus polymerase that may serve as a key factor in adaptation of influenza viruses from bat to nonbat host species. The PB2-282 residue, which harbors a highly conserved glutamic acid for influenza viruses across all genera (A, B, C, and D), encompasses an atypical serine in the case of bat influenza viruses. Our data show that the human-adapted polymerase, harboring a bat-specific signature (PB2-S282,) performs poorly, while bat PB2 protein, harboring a human-specific signature (PB2-E282), shows increased fitness in human cells.

Key Amino Acids of M1-41 and M2-27 Determine Growth and Pathogenicity of Chimeric H17 Bat Influenza Virus in Cells and in Mice.

Based on our previous studies, we show that the M gene is critical for the replication and pathogenicity of the chimeric H17 bat influenza virus (Bat09:mH1mN1) by replacing the bat M gene with those from human and swine influenza A viruses. However, the key amino acids of the M1 and/or M2 proteins that are responsible for virus replication and pathogenicity remain unknown. In this study, replacement of the PR8 M gene with the Eurasian avian-like M gene from the A/California/04/2009 pandemic H1N1 virus significantly decreased viral replication in both mammalian and avian cells in the background of the chimeric H17 bat influenza virus. Further studies revealed that M1 was more crucial for viral growth and pathogenicity than M2 and that the amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins identified in this study might be important for influenza virus surveillance and could be used to produce live attenuated vaccines in the future. IMPORTANCE The M1 and M2 proteins influence the morphology, replication, virulence, and transmissibility of influenza viruses. Although a few key residues in the M1 and M2 proteins have been identified, whether other residues of the M1 and M2 proteins are involved in viral replication and pathogenicity remains to be discovered. In the background of the chimeric H17 bat influenza virus, the Eurasian avian-like M gene from the A/California/04/2009 virus significantly decreased viral growth in mammalian and avian cells. Further study showed that M1 was implicated more than M2 in viral growth and pathogenicity in vitro and in vivo and that the key amino acid residues M1-41V and M2-27A were responsible for these characteristics in cells and in mice. These key residues of the M1 and M2 proteins could be used for influenza virus surveillance and live attenuated vaccine applications in the future. These findings provide important contributions to knowledge of the genetic basis of the virulence of influenza viruses.

Replication and virulence of chimeric bat influenza viruses in mammalian and avian cells and in mice

Previous studies have shown that chimeric bat influenza viruses can be generated by reverse genetic system. However, the roles of the surface or internal genes of chimeric bat influenza viruses in viral replication and virulence in different host species were still not completely understood. In this study, we generated a chimeric H9N2 bat virus with both HA and NA surface genes from the avian A2093/H9N2 virus and compared its replication and virulence with the chimeric H1N1 bat virus with both HA and NA from the PR8/H1N1 virus in vitro and in mice. The chimeric H1N1 virus showed significantly higher replication in mammalian and avian cells and significantly higher virulence in mice than the chimeric H9N2 virus. Moreover, the chimeric H9N2 virus with the bat influenza internal M gene showed a higher replication in mammalian cells than in avian cells. While the chimeric H9N2 virus with the avian-origin viral M gene displayed a higher replication than that with the bat influenza M gene in avian cells, which likely resulted from increased receptor binding ability to α 2,3 sialic acid linked glycans of the former virus. Our study indicates that bat influenza internal genes are permissive in both mammalian and avian cells, and the bat influenza internal M gene shows more compatibility in mammals than in the avian host. Although the surface genes play more critical roles for viral replication in different host substrates, influenza M gene also potentially impacts on replication, virulence and host tropism.

Egyptian Fruit Bats (Rousettus aegyptiacus) Were Resistant to Experimental Inoculation with Avian-Origin Influenza A Virus of Subtype H9N2, But Are Susceptible to Experimental Infection with Bat-Borne H9N2 Virus.

Influenza A viruses (IAV) of subtype H9N2, endemic in world-wide poultry holdings, are reported to cause spill-over infections to pigs and humans and have also contributed substantially to recent reassortment-derived pre-pandemic zoonotic viruses of concern, such as the Asian H7N9 viruses. Recently, a H9N2 bat influenza A virus was found in Egyptian fruit bats (Rousettus aegyptiacus), raising the question of whether this bat species is a suitable host for IAV. Here, we studied the susceptibility, pathogenesis and transmission of avian and bat-related H9N2 viruses in this new host. In a first experiment, we oronasally inoculated six Egyptian fruit bats with an avian-related H9N2 virus (A/layer chicken/Bangladesh/VP02-plaque/2016 (H9N2)). In a second experiment, six Egyptian fruit bats were inoculated with the newly discovered bat-related H9N2 virus (A/bat/Egypt/381OP/2017 (H9N2)). While R. aegyptiacus turned out to be refractory to an infection with H9N2 avian-type, inoculation with the bat H9N2 subtype established a productive infection in all inoculated animals with a detectable seroconversion at day 21 post-infection. In conclusion, Egyptian fruit bats are most likely not susceptible to the avian H9N2 subtype, but can be infected with fruit bat-derived H9N2. H9-specific sero-reactivities in fruit bats in the field are therefore more likely the result of contact with a bat-adapted H9N2 strain.

Bat Influenza Viruses: Current Status and Perspective.

Bats are natural reservoirs for many viruses, including several that are zoonotic. Two unusual H17N10 and H18N11 influenza viruses have been found in New World bats. Although neither of these viruses have been isolated, infectious clone technology has permitted significant progress to understand their biology, which include unique features compared to all other known influenza A viruses. In addition, an H9N2-like influenza A virus was isolated from Old World bats and it shows similar characteristics of normal influenza A viruses. In this review, current status and perspective on influenza A viruses identified in bats is reviewed and discussed.

Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge

Swine influenza is an important disease for the swine industry. Currently used whole inactivated virus (WIV) vaccines can induce vaccine-associated enhanced respiratory disease (VAERD) in pigs when the vaccine strains mismatch with the infected viruses. Live attenuated influenza virus vaccine (LAIV) is effective to protect pigs against homologous and heterologous swine influenza virus infections without inducing VAERD but has safety concerns due to potential reassortment with circulating viruses. Herein, we used a chimeric bat influenza Bat09:mH3mN2 virus, which contains both surface HA and NA gene open reading frames of the A/swine/Texas/4199–2/1998 (H3N2) and six internal genes from the novel bat H17N10 virus, to develop modified live-attenuated viruses (MLVs) as vaccine candidates which cannot reassort with canonical influenza A viruses by co-infection. Two attenuated MLV vaccine candidates including the virus that expresses a truncated NS1 (Bat09:mH3mN2-NS1-128, MLV1) or expresses both a truncated NS1 and the swine IL-18 (Bat09:mH3mN2-NS1-128-IL-18, MLV2) were generated and evaluated in pigs against a heterologous H3N2 virus using the WIV vaccine as a control. Compared to the WIV vaccine, both MLV vaccines were able to reduce lesions and virus replication in lungs and limit nasal virus shedding without VAERD, also induced significantly higher levels of mucosal IgA response in lungs and significantly increased numbers of antigen-specific IFN-γ secreting cells against the challenge virus. However, no significant difference was observed in efficacy between the MLV1 and MLV2. These results indicate that bat influenza vectored MLV vaccines can be used as a safe live vaccine to prevent swine influenza.

Tropism and neutralisation studies on bat influenza H17N10

The diversity of subtypes within Influenza A recently expanded with identification of H17N10 and H18N11 from bats. To study the tropism and zoonotic potential of these viruses, we successfully produced lentiviral pseudotypes bearing haemagglutinin H17 and neuraminidase N10. We investigated a range of cell lines from different species for their susceptibility to infection by these pseudotypes and show that a number of human haematopoietic cancer cell lines and the canine kidney MDCK II (but not MDCK I) cells are susceptible. Using microarrays and qRT-PCR we show that the dog leukocyte antigen DLA-DRA mRNA is over expressed in late passaged parental MDCK and commercial MDCK II cells, compared to early passaged parental MDCK and MDCK I cells, respectively. The human orthologue HLA-DRA encodes the alpha subunit of the MHC class II HLA-DR antigen-binding heterodimer. Small interfering RNA- or neutralizing antibody-targeting HLA-DRA, drastically reduced the susceptibility of Raji B cells to H17-PV. Conversely, over expression of HLA-DRA and its paralogue HLA-DRB1 on the surface of unsusceptible HEK293T/17 cells conferred susceptibility to H17-PV. The identification of HLA-DR as an H17N10 entry mediator will contribute to understanding the tropism of the virus and help to elucidate its zoonotic transmission. We also show that H17 pseudotypes can be efficiently neutralised by the broadly-neutralizing HA2 stalk monoclonal antibodies CR9114 and FI6. The lentiviral pseudotype system is a useful research tool, amenable for investigation of bat influenza tropism, restriction and pandemic preparedness, without safety issues of producing a replication-competent virus, to which the human population is naïve.

A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1

Highly pathogenic avian influenza viruses (HPAIVs) of subtype H5 are a major threat for poultry holdings worldwide, here especially the zoonotic Asian H5N1 viruses. These HPAIVs have caused more than 500 fatal spillover infections from poultry to humans, with a looming danger of a new pandemic by establishing human-to-human transmissions. Besides culling measures in infected farms in endemic areas, vaccination is the major tool against HPAIV. However, the mainly used inactivated preparations have several limitations, like application to the individual animal by injection and a reduced efficiency. Here we present a modified live influenza vaccine prototype, which is based on the H17N10 bat influenza virus. The new chimeric vaccine strain R65mono/H17N10 was able to provide full protection against a lethal challenge infection with HPAIV H5N1 of juvenile and subadult chickens, as well as ferrets after oronasal immunization. In addition, the H5 vaccine prototype cannot reassort with avian influenza viruses and therefore is a promising tool against HPAIV H5 infection, allowing new vaccination strategies for efficient disease control.

Bat Influenza Viruses: Making a Double Agent of MHC Class II.

MHC class II (MHCII) has recently been identified as a cellular receptor for bat influenza viruses. Here, we discuss the possible implications of viral exploitation of this critical host defense molecule and highlight the need for more intense study of bat–influenza virus interactions.

Mutations in the Neuraminidase-Like Protein of Bat Influenza H18N11 Virus Enhance Virus Replication in Mammalian Cells, Mice, and Ferrets.

To characterize bat influenza H18N11 virus, we propagated a reverse genetics-generated H18N11 virus in Madin-Darby canine kidney subclone II cells and detected two mammal-adapting mutations in the neuraminidase (NA)-like protein (NA-F144C and NA-T342A, N2 numbering) that increased the virus titers in three mammalian cell lines (i.e., Madin-Darby canine kidney, Madin-Darby canine kidney subclone II, and human lung adenocarcinoma [Calu-3] cells). In mice, wild-type H18N11 virus replicated only in the lungs of the infected animals, whereas the NA-T342A and NA-F144C/T342A mutant viruses were detected in the nasal turbinates, in addition to the lungs. Bat influenza viruses have not been tested for their virulence or organ tropism in ferrets. We detected wild-type and single mutant viruses each possessing NA-F144C or NA-T342A in the nasal turbinates of one or several infected ferrets, respectively. A mutant virus possessing both the NA-F144C and NA-T342A mutations was isolated from both the lung and the trachea, suggesting that it has a broader organ tropism than the wild-type virus. However, none of the H18N11 viruses caused symptoms in mice or ferrets. The NA-F144C/T342A double mutation did not substantially affect virion morphology or the release of virions from cells. Collectively, our data demonstrate that the propagation of bat influenza H18N11 virus in mammalian cells can result in mammal-adapting mutations that may increase the replicative ability and/or organ tropism of the virus; overall, however, these viruses did not replicate to high titers throughout the respiratory tract of mice and ferrets.IMPORTANCE Bats are reservoirs for several severe zoonotic pathogens. The genomes of influenza A viruses of the H17N10 and H18N11 subtypes have been identified in bats, but no live virus has been isolated. The characterization of artificially generated bat influenza H18N11 virus in mammalian cell lines and animal models revealed that this virus can acquire mammal-adapting mutations that may increase its zoonotic potential; however, the wild-type and mutant viruses did not replicate to high titers in all infected animals.

Bat influenza viruses transmit among bats but are poorly adapted to non-bat species.

Major histocompatibility complex class II (MHC-II) molecules of multiple species function as cell-entry receptors for the haemagglutinin-like H18 protein of the bat H18N11 influenza A virus, enabling tropism of the viruses in a potentially broad range of vertebrates. However, the function of the neuraminidase-like N11 protein is unknown because it is dispensable for viral infection or the release of H18-pseudotyped viruses. Here, we show that infection of mammalian cells with wild-type H18N11 leads to the emergence of mutant viruses that lack the N11 ectodomain and acquired mutations in H18. An infectious clone of one such mutant virus, designated rP11, appeared to be genetically stable in mice and replicated to higher titres in mice and cell culture compared with wild-type H18N11. In ferrets, rP11 antigen and RNA were detected at low levels in various tissues, including the tonsils, whereas the wild-type virus was not. In Neotropical Jamaican fruit bats, wild-type H18N11 was found in intestinal Peyer's patches and was shed to high concentrations in rectal samples, resulting in viral transmission to naive contact bats. Notably, rP11 also replicated efficiently in bats; however, only restored full-length N11 viruses were transmissible. Our findings suggest that wild-type H18N11 replicates poorly in mice and ferrets and that N11 is a determinant for viral transmission in bats.

Entry of the bat influenza H17N10 virus into mammalian cells is enabled by the MHC class II HLA-DR receptor.

Haemagglutinin and neuraminidase surface glycoproteins of the bat influenza H17N10 virus neither bind to nor cleave sialic acid receptors, indicating that this virus employs cell entry mechanisms distinct from those of classical influenza A viruses. We observed that certain human haematopoietic cancer cell lines and canine MDCK II cells are susceptible to H17-pseudotyped viruses. We identified the human HLA-DR receptor as an entry mediator for H17 pseudotypes, suggesting that H17N10 possesses zoonotic potential.