Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses. Previous studies indicated that a novel influenza A virus (H17N10) was circulating in fruit bats from Guatemala (Central America). Herein, we investigated whether similar viruses are present in bat species from South America. Analysis of rectal swabs from bats sampled in the Amazon rainforest region of Peru identified another new influenza A virus from bats that is phylogenetically distinct from the one identified in Guatemala. The genes that encode the surface proteins of the new virus from the flat-faced fruit bat were designated as new subtype H18N11. Serologic testing of blood samples from several species of Peruvian bats indicated a high prevalence of antibodies to the surface proteins. Phylogenetic analyses demonstrate that bat populations from Central and South America maintain as much influenza virus genetic diversity in some gene segments as all other mammalian and avian species combined. The crystal structures of the hemagglutinin and neuraminidase proteins indicate that sialic acid is not a receptor for virus attachment nor a substrate for release, suggesting a novel mechanism of influenza A virus attachment and activation of membrane fusion for entry into host cells. In summary, our findings indicate that bats constitute a potentially important reservoir for influenza viruses.

Antibody levels predict vaccine efficacy: Symptomatic COVID-19 infection can be prevented by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. A “correlate of protection” is a molecular biomarker to measure how much immunity is needed to fight infection and is key for successful global immunization programs. Gilbert et al . determined that antibodies are the correlate of protection in vaccinated individuals enrolled in the Moderna COVE phase 3 clinical trial (see the Perspective by Openshaw). By measuring binding and neutralizing antibodies against the viral spike protein, the authors found that the levels of both antibodies correlated with the degree of vaccine efficacy. The higher the antibody level, the greater the protection afforded by the messenger RNA (mRNA) vaccine. Antibody levels that predict mRNA vaccine efficacy can therefore be used to guide vaccine regimen modifications and support regulatory approvals for a broader spectrum of the population. —PNK

A group of neutralizing monoclonal antibodies (mAbs) targeting the influenza A hemagglutinin has been selected and characterized. Remarkably, these mAbs were able to neutralize a broad array of group 1 strains and could protect mice from infection when given prophylactically or therapeutically. The crystal structure of one such mAb in complex with hemagglutinin provides insight into its mechanism of neutralization and broad specificity. Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.

Influenza A virus reservoirs in animals have provided novel genetic elements leading to the emergence of global pandemics in humans. Most influenza A viruses circulate in waterfowl, but those that infect mammalian hosts are thought to pose the greatest risk for zoonotic spread to humans and the generation of pandemic or panzootic viruses. We have identified an influenza A virus from little yellow-shouldered bats captured at two locations in Guatemala. It is significantly divergent from known influenza A viruses. The HA of the bat virus was estimated to have diverged at roughly the same time as the known subtypes of HA and was designated as H17. The neuraminidase (NA) gene is highly divergent from all known influenza NAs, and the internal genes from the bat virus diverged from those of known influenza A viruses before the estimated divergence of the known influenza A internal gene lineages. Attempts to propagate this virus in cell cultures and chicken embryos were unsuccessful, suggesting distinct requirements compared with known influenza viruses. Despite its divergence from known influenza A viruses, the bat virus is compatible for genetic exchange with human influenza viruses in human cells, suggesting the potential capability for reassortment and contributions to new pandemic or panzootic influenza A viruses.

Aim: The A/goose/Guangdong/1/96‐like hemagglutinin (HA) genes of highly pathogenic avian influenza (HPAI) A(H5) viruses have continued to rapidly evolve since the most recent update to the H5 clade nomenclature by the WHO/OIE/FAO H5N1 Evolution Working Group. New clades diverging beyond established boundaries need to be identified and designated accordingly.Method: Hemagglutinin sequences deposited in publicly accessible databases up to December 31, 2014, were analyzed by phylogenetic and average pairwise distance methods to identify new clades that merit nomenclature changes.Results: Three new clade designations were recommended based on division of clade 2·1·3·2a (Indonesia), 2·2·1 (Egypt), and 2·3·4 (widespread detection in Asia, Europe, and North America) that includes newly emergent HPAI virus subtypes H5N2, H5N3, H5N5, H5N6, and H5N8.Conclusion: Continued global surveillance for HPAI A(H5) viruses in all host species and timely reporting of sequence data will be critical to quickly identify new clades and assess their potential impact on human and animal health.

In 2004, canine influenza virus subtype H3N8 emerged in greyhounds in the United States. Subsequent serologic evidence indicated virus circulation in dog breeds other than greyhounds, but the virus had not been isolated from affected animals. In 2005, we conducted virologic investigation of 7 nongreyhound dogs that died from respiratory disease in Florida and isolated influenza subtype H3N8 virus. Antigenic and genetic analysis of A/canine/Jacksonville/2005 (H3N8) and A/canine/Miami/2005 (H3N8) found similarity to earlier isolates from greyhounds, which indicates that canine influenza viruses are not restricted to greyhounds. The hemagglutinin contained 5 conserved amino acid differences that distinguish canine from equine lineages. The antigenic homogeneity of the canine viruses suggests that measurable antigenic drift has not yet occurred. Continued surveillance and antigenic analyses should monitor possible emergence of antigenic variants of canine influenza virus.