Researchers at Kanazawa University report in Nano Letters a high-speed atomic force microscopy study on a biological event that occurs when a flu virus enters and infects its host cell. The real-time visualization of influenza A hemagglutinin (HA) has enhanced the understanding of fusogenic transition of HA and its interactions with host exosomes.
Unlike living organisms, to avoid extinction, viruses need to hijack living host machineries to generate new viruses. The devastating respiratory virus, influenza A virus, utilize its hemagglutinin (HA) proteins to search for suitable host cells. Generally, HA has two important functions: selection of host cell and viral entry. Upon attaching to host cells, Influenza A virus are brought into host cells via endocytosis. A lipid bilayer cargo, known as endosome, carries influenza A virus from cell membrane into cytoplasm of host cell. Although the environment inside endosome is acidic, influenza A virus remains alive. More strikingly, HA undergoes structural change to mediate viral membrane to fuse with host endosomal membrane to form a hole in order to release viral components. Generation of this fusion event is elaborated as fusogenic, and hence structural changes of HA needed for this event is called as fusogenic transition. The mechanism of this event has been kept in Pandora’s Box for decades despite extensive studies have been done to reveal its mystery. Now, Keesiang Lim and Richard Wong from Kanazawa University and colleagues have studied the molecular dynamic of HA using high-speed atomic force microscopy, a technique enabling real-time visualization of molecules on the nanoscale. The researchers were not only able to record the fusogenic transition of HA, but also observe its interaction with exosomes (a lipid bilayer cargo similar to endosome released by cells to outside environment).
To study how HA can facilitate the fusion between viral membrane and host endosome membrane, Wong and colleagues let HA interacted with exosomes, a lipid bilayer cargo that mimics endosome. The HA-exosome interaction is expected to be similar to HA-endosome interaction during membrane fusion. During the interaction, conformational change of HA was found again before its docked on an exosome. Fusogenic transition releases a particular peptide, known as fusion peptide, which later inserts into the exosomal membrane, enabling the HA molecule to embed on the membrane. The scientists also found evidences that the HA-exosome interaction caused deformation or rupture of exosome, leading to a ‘leakage’ of exosomal materials.
Source – PR Newswire