Biology subjects

Wong, F. Y.

Publications and source records attributed to Wong, F. Y..

4 recordsLinked to original sources

bioRxiv2026

Haemagglutinin 162-164 deletions enhance influenza B/Victoria virus fitness and virulence in vivo

Influenza B viruses cause substantial respiratory disease and seasonal outbreaks. Despite decades of circulation in humans, only the B/Victoria lineage persisted after the COVID-19 pandemic. Continual evolution has generated hemagglutinin deletion variants at residues 162-164 that drive successive epidemics, yet their functional consequences remain poorly understood. Using integrated phylodynamics and reverse genetics, we show that Clade V1A.1 viruses carrying a two-amino acid deletion exhibit enhanced replication and increased virulence compared with ancestral viruses lacking deletions. The recently prevailing Clade V1A.3, which harbors a three-amino acid deletion together with the K136E substitution, has completely displaced V1A.1 and causes more severe disease in mice. Both clades bound efficiently to alpha 2-3 and 2-6 sialylated glycans and exhibited broad tolerance to acidic pH and elevated temperatures. These findings reveal that specific combinations of HA deletions and substitutions confer pronounced fitness advantages to emerging variants, driving global selective sweeps, evolutionary success and long-term persistence of B/Victoria lineage, and posing challenges for vaccine efficacy and influenza control.

microbiology↗

bioRxiv2024

Highly pathogenic avian influenza H5 virus exposure in goats and sheep

The recent outbreaks of highly pathogenic avian influenza A(H5N1) virus in North and South America, including widespread infection of cattle in the United States, calls for an urgent assessment of the host range of influenza A viruses, particularly for subtypes of pandemic concern. We conducted a serological survey for binding antibodies to influenza A and B viruses in goats (n=452) and sheep (n=329) in Pakistan and found high seropositive rates for the hemagglutinin (HA) of avian influenza A viruses (AIV) H5 (23.9-34.0%), H7 (13.9- 37.1%), and H9 (17.0-34.7%). In contrast, there were low levels of seropositivity against the HA of human and swine pandemic H1N1/pdm09 (0.9-1.8%) in goats and against swine H3 (0.6%) in sheep. Notably, we observed high reactivity to the neuraminidase of human H1N1/2009 (57.8-60.6%) and swine H3N2 (14.0-14.4%), likely due to cross-reactivity with the N1 and N2 proteins of H5N1 and H9N2 AIVs, respectively. Interestingly, we also detected seropositivity against influenza B HA in both goats (7.1%) and sheep (4.6%). The presence of AIV antibodies in goats and sheep suggest these species represent previously unrecognized hosts for viruses of pandemic concern, revealing extensive gaps in our current understanding of the ecology of influenza A and B viruses.

microbiology↗

bioRxiv2023

The genomic landscape of swine influenza A viruses in Southeast Asia

Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza virus (swIAV). Effective surveillance is essential to uncover emerging virus strains, however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia. By collecting more than 4,000 nasal swabs and 4,000 sera from pigs in Cambodia, we unmasked the co-circulation of multiple lineages of genetically diverse swIAV of pandemic concern. Genomic analyses revealed a novel European avian-like H1N2 swine reassortant variant with North American triple reassortant internal genes, that emerged approximately seven years before its first detection in pigs in 2021. Using phylogeographic reconstruction, we identified south central China as the dominant source of swine viruses disseminated to other regions in China and Southeast Asia. We also identified nine distinct swIAV lineages in Cambodia, which diverged from their closest ancestors between two to 15 years ago, indicating significant undetected diversity in the region, including reverse zoonoses of human H1N1/2009 pandemic and H3N2 viruses. A similar period of cryptic circulation of swIAVs occurred in the decades before the H1N1/2009 pandemic. The hidden diversity of swIAV observed here further emphasizes the complex underlying evolutionary processes present in this region, reinforcing the importance of genomic surveillance at the human-swine interface for early warning of disease emergence to avoid future pandemics.

microbiology↗

bioRxiv2021

Spike independent replication of human coronavirus in bat cells

Bats are the reservoir for numerous human pathogens including coronaviruses. The factors leading to the emergence and sustained transmission of coronaviruses in humans are poorly understood. An outstanding question is how coronaviruses can accomplish a host switch with a likely mismatch between the surface protein spike of a bat virus and the human cellular receptor at the time of zoonotic virus transmission. To identify potential novel evolutionary pathways for zoonotic virus emergence, we serially passaged six human 229E isolates in a newly established Rhinolophus lepidus (horseshoe bat) kidney cells and analyzed viral genetic changes. Here we observed extensive deletions within the spike and ORF4 genes of five 229E viruses after passaging in bat cells. As a result, spike protein expression and infectivity of human cells was lost in 5 of 6 viruses but the capability to infect bat cells was maintained. Only viruses that expressed the spike protein could be neutralized by 229E spike-specific antibodies in human cells, whereas there was no neutralizing effect on viruses that do not express the spike protein inoculated on bat cells. However, one isolate acquired an early stop codon abrogating spike expression but maintaining infection in bat cells. Upon passaging this isolate in human cells, spike expression was restored due to acquisition of nucleotide insertions amongst virus subpopulations. Spike-independent infection of coronaviruses provides an alternative mechanism for viral maintenance in bats that does not rely on the compatibility of viral surface proteins and cellular entry receptors.

microbiology↗