Pathogenesis of neurotropic herpesviruses: role of viral glycoproteins in neuroinvasion and transneuronal spread.

Neuroinvasion by herpesviruses requires entry into nerve endings in the periphery, transport to the cell body, replication in the cell body, axonal transport to the synapse and transneuronal viral spread. Entry occurs after receptor binding by fusion of virion envelope and cellular plasma membrane followed by microtubuli-assisted transport of capsids to the nuclear pore. By transneuronal spread, the virus gains access to synaptically linked neuronal circuits. A common set of herpesvirus glycoproteins is involved in entry and direct viral cell-cell spread. However, both processes can be distinguished by involvement of additional viral components. Interestingly, transneuronal spread appears to be functionally linked to intracytoplasmic formation of mature virions. This review will focus on the importance of herpesvirus envelope glycoproteins for infection of neurons and transneuronal spread, and their influence on viral pathogenesis.