Biology subjects

Dupre, G.

Publications and source records attributed to Dupre, G..

3 recordsLinked to original sources

bioRxiv2026

Mechanism-based prediction of insertion-driven high pathogenicity avian influenza virus emergence

High pathogenicity avian influenza viruses (HPAIVs) emerge from H5 and H7 low-pathogenicity avian influenza virus progenitors through mutations that introduce a multibasic cleavage site in haemagglutinin. Although nucleotide insertions recurrently generate this motif, the molecular determinants of insertion and whether particular HA sequences are genetically predisposed to evolve toward HPAIV remain unknown. Combining experimental virology and thermodynamic modelling, we show that insertions arise through polymerase slippage controlled by local product-template duplex thermodynamics within the viral polymerase catalytic site. Predicted RNA secondary structures outside the polymerase are not required for high-frequency insertions and only modestly modulate insertion rates. We formalize this mechanism in HPAIVpredict, which predicts insertion profiles, recapitulates intermediates associated with documented HPAIV emergence events and identifies H5 and H7 sequence backgrounds predisposed to acquire functional multibasic cleavage sites.

microbiology↗

bioRxiv2026

Sialic acids are a barrier to the entry of non-influenza orthomyxoviruses

Sialic acids (SAs) are abundantly expressed on vertebrate cell surfaces and are widely recognized as key viral attachment factors, particularly for influenza viruses. However, their role remains understudied in other orthomyxoviruses, such as thogoto and quaranja viruses, which are tick-borne viruses sporadically infecting humans. Enzymatic removal of SAs increased the infectivity of Thogoto and Dhori viruses, as well as pseudotypes carrying the glycoproteins of Oz, Sinu, and Wellfleet Bay viruses. A similar effect on pseudotype infectivity was observed following the binding of specific lectins to SAs. These findings indicate that, in contrast to influenza viruses, SAs act as a barrier to the entry of these orthomyxoviruses. Experimental evolution of the Sinu and Wellfleet Bay virus glycoproteins revealed point mutations that partially overcame this barrier. Given the abundance of sialic acids in mucosal tissues, we speculate that SAs may contribute to the inability of thogoto and quaranjaviruses to transmit directly between vertebrate hosts. Our results also underscore the importance of monitoring the circulation of these viruses for potential changes in their transmission routes. Author summaryMany viruses, including influenza viruses, use sugar molecules called sialic acids (SAs) on the surface of host cells to promote viral entry. Here, we show that SAs can instead restrict infection for several lesser-known relatives of influenza virus that are primarily transmitted by ticks and can occasionally infect humans. Removal of SAs from human cells strongly increased entry of these non-influenza viruses, when using both non-replicative pseudotypes and authentic viruses. In addition, masking SAs also enhanced entry of viral pseudotypes. We further found that viral surface proteins can acquire mutations that partially reduce this restriction, indicating an ability by these viruses to adapt to SA-rich environments. Because SAs are abundant in vertebrate mucosal tissues such as the respiratory tract, our findings suggest a possible explanation for why these viruses do not transmit directly between vertebrate hosts and rely on tick bites for infection. More broadly, this work identifies a previously unrecognized host cell surface feature that limits viral entry and highlights the importance of monitoring viral evolution that could alter transmission potential.

microbiology↗

bioRxiv2021

The strength of the innate immune response drives the within-host competition between highly and low pathogenic avian influenza viruses

Highly pathogenic avian influenza viruses (HPAIV) emerge from low pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse-genetics engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8LP increased H5N8HP replication and pathogenesis. By contrast, the H5N8LP antagonized H5N8HP replication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8LP, which correlated with H5N8HP inhibition. These data provide experimental evidence that HPAIV may be more likely to emerge in chickens than in ducks and underscore the importance of within-host viral variants interactions in viral evolution.

microbiology↗