Bone marrow-derived SH-SY5Y neuroblastoma cells infected with Kaposi's sarcoma-associated herpesvirus display unique infection phenotypes and growth properties

Kaposi's sarcoma-associated herpesvirus (KSHV) is an important oncogenic virus previously shown to be neurotropic, but studies on neuronal cell infection and pathogenesis are still very limited. Here, we characterized the effects of KSHV infection on neuronal SH-SY5Y cells by the recombinant virus rKSHV.219, which expresses both green fluorescent protein (GFP) and red fluorescent protein (RFP) to reflect the latent and lytic phases of infection. We demonstrated that infected cells have a higher growth rate and that KSHV infection can be sustained. Interestingly, the infected cells can transition spontaneously back and forth between lytic and latent phases of infection, producing progeny viruses but without any adverse effects on cell growth. In addition, transcriptome analysis of viral and cellular genes in latent and lytic cells showed that unlike other infected cell lines, the latently infected cells expressed both latent and most, but not all, of the lytic genes required for infectious virion production. The viral genes uniquely expressed by the lytic cells were mainly involved in the early steps of virus binding. Some of the cellular genes that were deregulated in both latently and lytically infected cells are involved in cell adhesion, cell signal pathways, and tumorigenesis. The downregulated cellular CCDN1, PAX5, and NFASC and upregulated CTGF, BMP4, YAP1, LEF1, and HLA-DRB1 genes were found to be associated with cell adhesion molecules (CAMs), hippo signaling, and cancer. These deregulated genes may be involved in creating an environment that is unique in neuronal cells to sustain cell growth upon KSHV infection and not observed in other infected cell types.