A team from Huazhong Agricultural University (HZAU) published a research paper titled "Rab27a regulates the transport of influenza virus membrane proteins to the plasma membrane" in the journal Nature Communications on July 8.
The research reveals the molecular mechanism of transporting influenza virus membrane proteins to budding sites after synthesis, thus contributing to virus particle assembly and budding.
The highly infectious and rapidly spreading Influenza A Virus (IAV) relies on the enrichment of membrane proteins (including Hemagglutinin [HA], Neuraminidase [NA], and Matrix Protein 2 [M2]) and the positioning of viral ribonucleoprotein (vRNP) complexes at budding sites as necessary conditions to trigger virus budding, but the mechanism of membrane protein transport was previously unclear.

Rab27a and its effector molecules SYTL1/4 regulate the transport of influenza virus membrane proteins. [Photo/news.hzau.edu.cn]
The study used siRNA to target different Rab GTPases involved in Golgi processing and transport and identified Rab27a as a key host factor regulating the cell surface levels of the HA protein during influenza virus infection. Further research revealed that the GTP-bound form of Rab27a mediates the transport of virus membrane proteins HA, NA, and M2 to the cell surface, promoting the assembly and budding process of the influenza virus. Through the use of the RUSH (retention using selective hooks) system, the transport pathway was visualized, showing that Rab27a regulates transport through positive vesicles, and its function depends on the effector molecules SYTL1 and SYTL4, with SYTL4 playing a predominant role. Notably, in a mouse challenge model, silencing SYTL4 provided a higher protective rate compared to silencing Rab27a, indicating the potential of SYTL4 as a target for anti-influenza virus drugs.