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Debby van Riel @debbyvanriel.bsky.social · 08/04/2025

In the white matter of the cerebral cortex and the CA1 region of the hippocampus there was a decrease in the GFAP+ surface area (decrease of astrocyte actication). In the hippocampus this was associated with an increase of IBA1+ surface area.

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Debby van Riel @debbyvanriel.bsky.social · 08/04/2025

In the olfactory bulb there was no evidence for an increase of microglia compared to mock inoculated ferrets, although the surface area of IBA1+ cells was increased (suggestive for microglial activation). There was no increase of astrocytes.

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Debby van Riel @debbyvanriel.bsky.social · 08/04/2025

In the brain we did not detect histological changes associated with inflammation, gliosis or necrosis. However, we did detect an increase of Alzheimer type II astrocytes in the pons and cerebellum at 7 and 21 dpi compared to mock inoculated ferrets.

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Debby van Riel @debbyvanriel.bsky.social · 08/04/2025

From intranasally inoculated ferrets, noses and brains were collected 7 and 21 days post inoculation (dpi). Virus antigen was detected sporadically in the nose at 7 dpi in respiratory and olfactory mucosa. In the brain we only detected viral RNA at 7 dpi, with high ct values.

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Debby van Riel @debbyvanriel.bsky.social · 02/12/2024

7/ Finally clade 2.3.4.4b H5N1 virus infection triggered in a type-I and -III IFN response. Of the measured pro-inflammatory cytokines only IP-10 could be detected, and f.e. not IL-6 and TNF, which was detected in the H3N2 virus infected cultures.

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Debby van Riel @debbyvanriel.bsky.social · 02/12/2024

6/ The polymerase activity of 2.3.4.4b H5N1 virus was not higher than that of H5N1-2005 virus. The more efficient replication of 2.3.4.4b H5N1 virus in human epithelial cells was thus not associated with an increased polymerase activity.

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Debby van Riel @debbyvanriel.bsky.social · 02/12/2024

5/ Infection was predominantly seen in ciliated epithelial cells. Abundant infection of clade 2.3.4.4b H5N1 virus in tr/br cultures resulted in loss of cilia, however, tight junctions stayed intact (based on ZO-1 expression). ZO-1 expression decreased in H3N2 infected cultures.

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Debby van Riel @debbyvanriel.bsky.social · 02/12/2024

4/ Without attachment no infection, but attachment alone is not sufficient. In vitro, 2.3.4.4b H5N1 virus replicated to higher titers in both nasal and trachea/bronchial epithelial cells than H5N1-2005. In the tracheal/bronchial epithelial cells even to similar titers as a H3N2 virus.

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Debby van Riel @debbyvanriel.bsky.social · 02/12/2024

4/ In the lower respiratory tract clade 2.3.3.4b H5 virus attached more abundantly to the ciliated epithelial cells in the trachea, bronchus and bronchioles than 2.3.2.1 H5 virus, but not as abundant as a seasonal H3N2 virus

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Debby van Riel @debbyvanriel.bsky.social · 02/12/2024

3/First we showed that clade 2.3.4.4b H5 virus attached more abundantly to both the human upper and lower respiratory tract than a well-studied clade 2.3.2.1 H5 virus from 2005. However, attachment was not as abundant as an human H3N2 virus in the nasal turbinates.

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