Post by Nadica (She/Her) on Dec 11, 2024 1:44:25 GMT
H5 subtype avian influenza virus induces Golgi apparatus stress response via TFE3 pathway to promote virus replication - Published Dec 9, 2024
Abstract
During infection, avian influenza virus (AIV) triggers endoplasmic reticulum (ER) stress, a well-established phenomenon in previous research. The Golgi apparatus, situated downstream of the ER and crucial for protein trafficking, may be impacted by AIV infection. However, it remains unclear whether this induces Golgi apparatus stress (GAS) and its implications for AIV replication. We investigated the morphological changes in the Golgi apparatus and identified GAS response pathways following infection with the H5 subtype AIV strain A/Mallard/Huadong/S/2005. The results showed that AIV infection induced significant swelling and fragmentation of the Golgi apparatus in A549 cells, indicating the presence of GAS. Among the analyzed GAS response pathways, TFE3 was significantly activated during AIV infection, while HSP47 was activated early in the infection process, and CREB3-ARF4 remained inactive. The blockade of the TFE3 pathway effectively inhibited AIV replication in A549 cells and attenuated AIV virulence in mice. Additionally, activation of the TFE3 pathway promoted endosome acidification and upregulated transcription levels of glycosylation enzymes, facilitating AIV replication. These findings highlight the crucial role of the TFE3 pathway in mediating GAS response during AIV infection, shedding light on its significance in viral replication.
Author summary
Influenza virus infection is known to trigger the endoplasmic reticulum stress response, a critical cellular reaction. The Golgi apparatus, positioned downstream of the endoplasmic reticulum, plays a vital role in protein modification and trafficking. Our study demonstrated that avian influenza virus (AIV) infection indeed induced GAS, as evidenced by the swelling and fragmentation of the Golgi apparatus observed in A549 cells. Moreover, the TFE3 pathway was significantly activated in response to GAS during AIV infection, which facilitates viral replication by enhancing endosome acidification and promoting the transcription of glycosylation enzymes. Inhibition of the TFE3 pathway significantly impeded AIV replication and decreased viral pathogenicity, suggesting its potential as a broad-spectrum target for antiviral drug development. These findings provide the first evidence linking AIV replication with GAS response, thereby advancing our understanding of AIV replication mechanisms.
Abstract
During infection, avian influenza virus (AIV) triggers endoplasmic reticulum (ER) stress, a well-established phenomenon in previous research. The Golgi apparatus, situated downstream of the ER and crucial for protein trafficking, may be impacted by AIV infection. However, it remains unclear whether this induces Golgi apparatus stress (GAS) and its implications for AIV replication. We investigated the morphological changes in the Golgi apparatus and identified GAS response pathways following infection with the H5 subtype AIV strain A/Mallard/Huadong/S/2005. The results showed that AIV infection induced significant swelling and fragmentation of the Golgi apparatus in A549 cells, indicating the presence of GAS. Among the analyzed GAS response pathways, TFE3 was significantly activated during AIV infection, while HSP47 was activated early in the infection process, and CREB3-ARF4 remained inactive. The blockade of the TFE3 pathway effectively inhibited AIV replication in A549 cells and attenuated AIV virulence in mice. Additionally, activation of the TFE3 pathway promoted endosome acidification and upregulated transcription levels of glycosylation enzymes, facilitating AIV replication. These findings highlight the crucial role of the TFE3 pathway in mediating GAS response during AIV infection, shedding light on its significance in viral replication.
Author summary
Influenza virus infection is known to trigger the endoplasmic reticulum stress response, a critical cellular reaction. The Golgi apparatus, positioned downstream of the endoplasmic reticulum, plays a vital role in protein modification and trafficking. Our study demonstrated that avian influenza virus (AIV) infection indeed induced GAS, as evidenced by the swelling and fragmentation of the Golgi apparatus observed in A549 cells. Moreover, the TFE3 pathway was significantly activated in response to GAS during AIV infection, which facilitates viral replication by enhancing endosome acidification and promoting the transcription of glycosylation enzymes. Inhibition of the TFE3 pathway significantly impeded AIV replication and decreased viral pathogenicity, suggesting its potential as a broad-spectrum target for antiviral drug development. These findings provide the first evidence linking AIV replication with GAS response, thereby advancing our understanding of AIV replication mechanisms.