Abstract
Members of the family Orthoherpesviridae employs two distinct transmission modes: free virion release and cell-to-cell transmission. The latter enables immune evasion through multiple mechanisms, facilitating infections in skin, mucosa, and neural tissues. This review synthesizes current knowledge on human herpesvirus cell-to-cell transmission mechanisms, including syncytium formation, tight junction exploitation, exosomal transfer, and tunneling nanotube utilization. We analyze how these strategies enhance infection efficiency, evade immune surveillance, and augment pathogenicity. Furthermore, we discuss recent intervention strategies targeting cell-to-cell transmission, including the development of monoclonal antibodies, antiviral drugs, and vaccines. These inights provide a theoretical foundation for developing novel approaches against human herpesvirus infections.