Models of HSV-1 entry into host cells. (IMAGE)
Caption
(i) Direct fusion pathway: HSV-1 initially attaches to the host cell surface via the binding of gC and/or gB to heparan sulfate proteoglycans (HSPGs). This attachment is followed by the binding of gD to its specific receptors, such as nectin-1. The receptor binding induces a conformational change in gD, transitioning it from a self-inhibited state to an active conformation that exposes its pre-fusion domain (PFD). This activation signal is transmitted to the gH/gL heterodimer. Concurrently, the gH/gL complex binds to integrin receptors on the host cell surface, causing the dissociation of gL from the complex and activating gH. Activated gH interacts with the cytoplasmic domain (CTD) of gB, triggering a conformational shift in gB from its pre-fusion to post-fusion state. This shift facilitates the fusion of the viral envelope with the host cell membrane, releasing the viral DNA into the host nucleus to initiate replication.
(ii) Endocytic pathway: In some cell types, the gH/gL complex activates integrin receptors, promoting viral endocytosis through signaling via the C-terminal tail of the integrin β subunit. Within the acidic environment of the endosome, gB is activated, facilitating the fusion of the viral envelope with the endosomal membrane. This process releases the viral capsid and tegument proteins into the cytoplasm. The viral DNA is subsequently transported to the nucleus, where it initiates transcription and replication. The figure was created with BioRender.com
Credit
Yufang Zou, Juan Tao, Yingzheng Gao, Jixuan Wang, Pengfei Wang, Jingyuan Yan, Zuqing Nie, Dewei Jiang, Xinwei Huang
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