“…In the study using APOE4 knockout mice, Burgos et al (2006) detected significant lower HSV-1 genomes in the nervous system than that in the wildtype mice, suggesting that APOE4 facilitates HSV-1 invasion and latency establishment in the brain. Later, by examining key steps of HSV-1 lytic replication, Liu et al (2023) surprisingly demonstrated that APOE4 protein inhibits HSV-1 attachment but not viral entry, replication, assembly, or intracellular transportation of lytic replication, which may contribute to the enhanced latency. Paradoxically, APOE4 can be incorporated into HSV-1 virions to promote viral release from cell membrane ( Liu et al, 2023 ).…”