Bovine herpesvirus 4 infects differentiated neuronal cells in culture and establish persistent infection upon selection.

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus with no clear disease association. Although BoHV-4 is not considered a neurotropic virus, it has been detected in peripheral and/or central nervous system tissues during persistent infection (Lopez et al, 1996, Microb Pathogen 21: 47-58; Yamamoto et al, 2000, Arch Virol 145: 2363-2370; Asano et al, 2003, J Vet Med Sci 65: 87-93). However, the direct interaction between BoHV-4 and neurons has not been studied so far. The authors investigated the interaction of BoHV-4 with N2a (neuroblastoma cell line) cells through the use of two recombinant viruses (BoHV-4/26A3 neo and BoHV-4EGFP?TK). Because of the unique biological characteristics of N2a cells, which differentiate in neuron-like cells producing dendrites, axon, and specific neuronal markers, the authors found that BoHV-4 infects differentiated N2a cells and a persistent infection can be established. BoHV-4 persistently infected N2a cells produce infectious viral particles, which do not interfere with cellular differentiation.