Collectively, these studies strongly improve our general understanding of virus-induced changes in the proteome, metabolome and metabolite distribution in host tissues of humans, animals and plants upon infection. Furthermore, latest MSI research provided important insights into the drug distribution and distribution kinetics, especially in antiretroviral research. Finally, MSI-based investigations of oncogenic viruses greatly increased our knowledge on tumor mass signatures and facilitated the identification of cancer biomarkers.The DNA viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are members of the gammaherpesvirus subfamily, a group of viruses whose infection is associated with multiple malignancies, including cancer. The primary host for these viruses is humans and, like all herpesviruses, infection with these pathogens is lifelong. Due to the persistence of gammaherpesvirus infection and the potential for cancer formation in infected individuals, there is a driving need to understand not only the biology of these viruses and how they remain undetected in host cells but also the mechanism(s) by which tumorigenesis occurs. One of the methods that has provided much insight into these processes is proteomics. Proteomics is the study of all the proteins that are encoded by a genome and allows for (i) identification of existing and novel proteins derived from a given genome, (ii) interrogation of protein-protein interactions within a system, and (iii) discovery of druggable targets for the treatment of malignancies. https://www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html In this chapter, we explore how proteomics has contributed to our current understanding of gammaherpesvirus biology and their oncogenic processes, as well as the clinical applications of proteomics for the detection and treatment of gammaherpesvirus-associated cancers.The vertebrate innate immune system confers host cells with mechanisms to protect against both evolutionarily ancient pathogens and newly emerging pathogenic strains. Innate immunity relies on the host cell's ability to distinguish between self and pathogen-derived molecules. To achieve this, the innate immune system uses germline encoded receptors called pattern recognition receptors (PRRs), which recognize various molecular signatures, including nucleic acids, proteins, lipids, glycans and glycolipids. Among these molecules, the recognition of pathogenic, mislocalized, or damaged DNA by cellular protein receptors, commonly called DNA sensors, represents a major surveillance pathway for initiating immune signaling. The ability of cells to temporally regulate DNA sensor activation and subsequent signal termination is critical for effective immune signaling. These same mechanisms are also co-opted by pathogens to promote their replication. Therefore, there is significant interest in understanding DNA sensor regulatory networks during microbial infections and autoimmune disease. One emerging aspect of DNA sensor regulation is through post-translational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, ADP-ribosylation, SUMOylation, methylation, deamidation, glutamylation. In this chapter, we discuss how PTMs have been shown to positively or negatively impact DNA sensor functions via diverse mechanisms, including direct regulation of enzymatic activity, protein-protein and protein-DNA interactions, protein translocations and protein turnover. In addition, we highlight the ability of virus-induced PTMs to promote immune evasion. We also discuss the recent evidence linking PTMs on DNA sensors with human diseases and more broadly, highlight promising directions for future research on PTM-mediated regulation of DNA sensor-dependent immune signaling.Proteases precisely and irreversibly catalyze the hydrolysis of peptide bonds, regulating the fate, localization, and activity of many proteins. Consequently, proteolytic activity plays an important role in fundamental cellular processes such as differentiation and migration, immunological and inflammatory reactions, apoptosis and survival. During virus infection, host proteases are involved in several processes, from cell entry to initiation, progression and resolution of inflammation. On the other hand, many viruses encode their own highly specific proteases, responsible for the proteolytic processing of viral proteins, but, at the same time, to cleave host proteins to corrupt antiviral host responses and adjust protein activity to favor viral replication. Traditionally, protease substrate identification has been addressed by means of hypothesis-driven approaches, but recent advances in proteomics have made a toolkit available to uncover the extensive repertoire of host proteins cleaved during infection, either by viral or host proteases. Here, we review the currently available proteomics-based methods that can and have contributed to the systematic and unbiased identification of new protease substrates in the context of virus-host interactions. The role of specific proteases during the course of virus infections will also be highlighted.The cellular surfaceome and its residing extracellularly exposed proteins are involved in a multitude of molecular signaling processes across the viral infection cycle. Successful viral propagation, including viral entry, immune evasion, virion release and viral spread rely on dynamic molecular interactions with the surfaceome. Decoding of these viral-host surfaceome interactions using advanced technologies enabled the discovery of fundamental new functional insights into cellular and viral biology. In this review, we highlight recently developed experimental strategies, with a focus on spatial proteotyping technologies, aiding in the rational design of theranostic strategies to combat viral infections.The host cell proteome undergoes a variety of dynamic changes during viral infection, elicited by the virus itself or host cell defense mechanisms. Studying these changes on a global scale by integrating functional and physical interactions within protein networks during infection is an important tool to understand pathology. Indeed, proteomics studies dissecting protein signaling cascades and interaction networks upon infection showed how global information can significantly improve understanding of disease mechanisms of diverse viral infections. Here, we summarize and give examples of different experimental designs, proteomics approaches and bioinformatics analyses that allow profiling proteome changes and host-pathogen interactions to gain a molecular systems view of viral infection.