A team led by professor Zhou Hongbo at Huazhong Agricultural University (HZAU) has uncovered a critical host protein that regulates influenza virus trafficking and uncoating within cells, offering new insights into antiviral strategies. The findings were published June 5 in Advanced Science under the title Adducin-1 Facilitates Influenza Virus Endosomal Trafficking and Uncoating by Regulating Branched Actin Dynamics and Myosin IIB Activity.

Influenza A virus (IAV), a major zoonotic pathogen, poses a serious threat to both animal farming and global public health.

Like many enveloped viruses, IAV hijacks the host's actin cytoskeleton to enter and move within cells. However, the host factors involved in its intracellular transport remained largely unknown.

Using CRISPR screening and real-time virus tracking with quantum dot labeling, Zhou's team identified Adducin-1 (ADD1) as an essential host protein for IAV infection. Researchers found that ADD1 regulates actin remodeling and enables the virus to transition from the cell membrane to RAB5 and RAB7-positive endosomes. Loss of ADD1 causes actin overbranching, trapping the virus near the plasma membrane.

Further experiments showed that IAV infection induces phosphorylation of ADD1 at Ser726, promoting actin depolymerization and facilitating viral transport and fusion with early endosomes. The same phosphorylation pattern was observed in other endosome-trafficking viruses, such as VSV and PEDV.

Additionally, ADD1 regulates mechanical force generation during viral uncoating through the RhoA/MLC/myosin IIB pathway. Knocking down ADD1 or injecting the WASP activator EG-011 significantly suppressed IAV replication in mice and improved survival, highlighting ADD1 as a promising antiviral target.

ADD1 regulates endosomal trafficking and uncoating of influenza virus. [Photo/news.hzau.edu.cn]