Omics-Level Approaches to Studying Gammaherpesvirus Infection

Gammaherpesviruses (GHVs) represent a global clinical burden as the causative agents of Kaposi's sarcoma and mononucleosis, among other diseases. Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are the most studied human GHVs, and murine gammaherpesvirus 68 (MHV-68) is a recognized experimental model. GHVs are defined by their modulation of the host cell to establish lifelong latent infections and increase host dysregulation during periodic reactivation. Due to their ubiquitous changes in host cells, systems-level techniques are well-suited to study GHV infections at all stages of the central dogma: genomics, transcriptomics, and proteomics. Furthermore, metabolomics can reveal the final metabolic changes across numerous host cellular pathways. This review assesses the current knowledge on GHV infections gained through omics techniques. We also identify gaps and propose future directions, including the development of new therapeutic strategies. Early omics techniques have characterized large swaths of infection for EBV, KSHV, and MHV-68, revealing conserved genes, homologous transcripts, and proteins. Modern omics techniques have enabled higher-resolution studies, yielding insights into heterogeneity in viral-host gene, transcript, and protein modulation strategies across geographical populations, viral subtypes, inter- and intra-patient infections, and latent and lytic states. The metabolome during GHV infections remains the least understood, but current studies have identified essential modulations of nucleotide, amino acid, and lipid synthesis by EBV, KSHV, and MHV-68. Importantly, the application of integrative omics methods to GHV infections remains a promising direction of study as the increased resolution of modern techniques meets the need for greater understanding of differences in each GHV infection.