Ashok, A. K. | Search bioRxiv

bioRxiv2024

Decoding non-human mammalian adaptive signatures of 2.3.4.4b H5N1 to assess its human adaptive potential

The recent panzootic 2.3.4.4b clade H5N1 infected diverse non-human mammalian species globally, showed mammal-to-mammal transmission among them and caused sporadic human infections. However, whether 2.3.4.4b H5N1 circulating in non-human mammals can establish human infections and spread among humans is unclear. Gain-of-function research restrictions preclude assessing human adapting mutations of 2.3.4.4b H5N1. Here, we tracked the evolution of 2.3.4.4b H5N1 that infected non-human mammals and evaluated their ability to gain human adaptations. The non-human mammal 2.3.4.4b H5N1 partly acquired classical human adapting mutations, which are identical to the residues of H1N1pdm09 and seasonal human H3N2 infections while showing a few species-specific adaptations that might be potential barriers for successful human adaptations. Despite minimal changes in Hemagglutinin (HA), A160T and T199I mutations near the receptor binding site of HA in dairy cattle viruses indicate the rapid HA glycan surface evolution affecting virus entry and immune evasion. The quantitative assessment indicated that 2.3.4.4b H5N1 circulating in bears, cattle, dolphins, and foxes show higher human adaptive potential than other hosts. Also, H5N1 infections in mammals across time showed a unique set of adaptations in the 2.3.4.4b clade compared to previously circulating strains, especially the acquisition of Q591 adaptation in PB2 that enables human adaptation. Thus, 2.3.4.4b H5N1 acquires human adaptations due to natural selection pressure in non-human mammals. Overall, our study delineates human adaptation and infection risk of specific non-human mammalian circulating HPAI 2.3.4.4b H5N1 strains. O_FIG O_LINKSMALLFIG WIDTH=164 HEIGHT=200 SRC="FIGDIR/small/609722v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@2dde4borg.highwire.dtl.DTLVardef@15d4983org.highwire.dtl.DTLVardef@1857093org.highwire.dtl.DTLVardef@1a1eec2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACTC_FLOATNO C_FIG

microbiology↗

bioRxiv2024

Monkeys engage in visual simulation to solve complex problems

Visual simulation -- i.e., using internal reconstructions of the world to experience potential future versions of events that are not currently happening -- is among the most sophisticated capacities of the human mind. But is this ability in fact uniquely human? To answer this question, we tested monkeys on a series of experiments involving the Planko game, which we have previously used to evoke visual simulation in human participants. We found that monkeys were able to successfully play the game using a simulation strategy, predicting the trajectory of a ball through a field of planks while demonstrating a level of accuracy and behavioral signatures comparable to humans. Computational analyses further revealed that the monkeys strategy while playing Planko aligned with a recurrent neural network (RNN) that approached the task using a spontaneously learned simulation strategy. Finally, we carried out awake functional magnetic resonance imaging while monkeys played Planko. We found activity in motion-sensitive regions of the monkey brain during hypothesized simulation periods, even without any perceived visual motion cues. This neural result closely mirrors previous findings from human research, suggesting a shared mechanism of visual simulation across species. In all, these findings challenge traditional views of animal cognition, proposing that nonhuman primates possess a complex cognitive landscape, capable of invoking imaginative and predictive mental experiences to solve complex everyday problems.

neuroscience↗