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Associating bovine herpesvirus 1 envelope glycoprotein gD with activated phospho-PLC-γ1(S1248)
Chang Liu1, Weifeng Yuan2, Hao Yang1
1College of Life Sciences, Hebei University , Baoding, China.
Insights
Bovine herpesvirus 1 infection activates phospholipase C gamma 1 (PLC-γ1) signaling, leading to its accumulation in the Golgi apparatus. This activated PLC-γ1 escorts viral particles for release, revealing a novel mechanism in virus replication.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Phospholipase C gamma 1 (PLC-γ1) is known to localize in various cellular compartments, including the cytosol, plasma membrane, and nucleus.
- Bovine herpesvirus 1 (BoHV-1) productive infection is associated with increased levels of phosphorylated PLC-γ1 at Ser1248 (p-PLC-γ1(S1248)), which supports viral replication.
Purpose of the Study:
- To investigate the subcellular localization of activated p-PLC-γ1(S1248) during BoHV-1 infection.
- To elucidate the role of p-PLC-γ1(S1248) in the BoHV-1 life cycle, particularly in relation to viral particle trafficking.
Main Methods:
- Confocal microscopy to visualize p-PLC-γ1(S1248) localization in infected cells.
- Coimmunoprecipitation assays to identify proteins interacting with Golgi-localized p-PLC-γ1(S1248).
- Treatment with a PLC-γ1-specific inhibitor (U73122) to assess the functional role of PLC-γ1 signaling in viral egress.
Main Results:
- Activated p-PLC-γ1(S1248) was found to accumulate in the Golgi apparatus during later stages of BoHV-1 infection.
- Golgi-associated p-PLC-γ1(S1248) specifically binds to the viral protein gD, but not gC.
- Inhibition of PLC-γ1 signaling led to the retention of viral protein gD within the Golgi apparatus, suggesting impaired virion egress.
Conclusions:
- This study identifies the Golgi apparatus as a novel cellular compartment containing activated p-PLC-γ1(S1248) during BoHV-1 infection.
- Activated p-PLC-γ1(S1248) is associated with both intracellular and released virions, and its interaction with gD suggests a role in viral particle transport.
- PLC-γ1 signaling appears to facilitate the trafficking of progeny virions from the Golgi apparatus, representing a new mechanism in BoHV-1 productive infection.
Importance:
Bovine herpesvirus 1 (BoHV-1) productive infection increases protein levels of phosphorylated-phospholipase C gamma 1 at Ser1248 [p-PLC-γ1(S1248)]. However, whether it causes any variations to p-PLC-γ1(S1248) localization is not well understood. Here, for the first time, we found that partial p-PLC-γ1(S1248) is residing in the Golgi apparatus, where the accumulation is enhanced by virus infection. p-PLC-γ1(S1248) is consistently associated with virions, partially via binding to gD, in both the Golgi apparatus and cytoplasm membranes. Surprisingly, it also associates with the released virions. Of note, this is the first evidenced BoHV-1 virion-bound host protein. It seems that p-PLC-γ1(S1248) works as an escort during trafficking of progeny virions out of Golgi apparatus to the plasma membranes as well as releasing outside of the cell membranes. Furthermore, we showed that the activated p-PLC-γ1(S1248) is potentially implicated in the transport of virions out of Golgi apparatus, which may represent a novel mechanism to regulate virus productive infection.
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