Contribution of MS-Based Proteomics to the Understanding of Herpes Simplex Virus Type 1 Interaction with Host Cells

Abstract

Like other DNA viruses, herpes simplex virus type 1 (HSV-1) replicates and proliferates in host cells continuously modulating the host molecular environment. Following a sophisticated temporal expression pattern, HSV-1 encodes at least 89 multifunctional proteins that interplay with and modify the host cell proteome. During the last decade, advances in mass spectrometry applications coupled to the development of proteomic separation methods have allowed to partially monitor the impact of HSV-1 infection in human cells. In this review, we discuss the current use of different proteome fractionation strategies to define HSV-1 targets in two major application areas: (i) viral-protein interactomics to decipher viral-protein interactions in host cells and (ii) differential quantitative proteomics to analyze the virally induced changes in the cellular proteome. Moreover, we will also discuss the potential application of high-throughput proteomic approaches to study global proteome dynamics and also post-translational modifications in HSV-1-infected cells that will greatly improve our molecular knowledge of HSV-1 infection.

Quantification of the Host Response Proteome after Herpes Simplex Virus Type 1 Infection

“…Proteomic approaches to studying virus infections are becoming more accurate and effective, especially with the advantages of high throughput methodologies such as mass spectrometry . There are many different approaches to studying proteomics in virus infections, including proteomics of virus particles (structure or host proteins inside the virus), viral protein interactomics, and changes to the host cell proteome upon viral infection. , There has been a variety of HSV proteomic research to date, such as identifying host proteins that interact with specific viral proteins, identifying all of the virus proteins in a mature virus particle and the nonstructural proteins present in host cells during infection, identifying host proteins present in mature virion tegument, detecting host protein changes in specific cellular compartments such as ribosomes, microsomes, and the nucleus, examining the macrophage secretome of infected cells and finally host cell extract analysis . However, as was recently reviewed, there are still many gaps in our knowledge of the virus–host proteomic interaction, including global protein dynamics and quantitative profiling of host proteins during infection.…”

Proteomics Analysis of Herpes Simplex Virus Type 1-Infected Cells Reveals Dynamic Changes of Viral Protein Expression, Ubiquitylation, and Phosphorylation

“…Previous proteomics analyses of herpes viruses have focused on identifying components of mature and immature viral particles − and on changes of the host cell proteome or macrophage secretome induced by infection. − Here, we performed a comprehensive quantitative analysis of the HSV1 proteome of infected cells with and without inhibition of DNA replication. Furthermore, we analyzed the HSV1 proteome for the presence of modified residues and identified 90 novel phosphorylation and 10 novel ubiquitylation sites on HSV1 proteins.…”

Mass Spectrometry-Based Proteomic Approaches for Discovery of HIV–Host Interactions

“…They have evolved to manipulate the cellular machinery, evade the host immune response and hijack signaling pathways for their own benefit. Identification of those requisite cellular factors is invaluable to gain an intimate understanding of viral invasion and host defense strategies, as exampled by recent proteomic studies of influenza A [1], hepatitis C virus [2] and herpes simplex virus type 1 [3]. It would also provide potential targets for antiviral intervention, particularly for viruses causing pandemic diseases such as HIV-1, the major focus of this review.…”