Post-Translational Modifications in Viruses
Post-translational modifications (PTMs) are chemical modifications that occur on amino acid residues after protein synthesis, regulating protein structure, localization, and function. Viruses rely on the host PTM system to complete entry, replication, assembly, and immune evasion, while the dynamic changes of these modifications can be comprehensively mapped through modern proteomics approaches. Mass spectrometry–based proteomics enables researchers to capture PTM sites, modification patterns, and their temporal dynamics during infection on a large scale, providing critical insights into the mechanisms of viral pathogenesis.
Zhao, X. et al. Front Microbiol. 2024.
Common PTMs in Viruses
1. Glycosylation
Glycosylation is the most prominent modification of viral envelope proteins, directly determining infectivity and immune evasion. Glycans help newly synthesized proteins fold correctly and remain stable, preventing misfolding and degradation. Specific glycosylation sites enhance the affinity of viral proteins for host receptors, shaping host range and cross-species transmission. Dense glycan shields can mask critical epitopes, limiting neutralizing antibody binding and weakening host immune responses. Even subtle changes in glycosylation patterns, or heterogeneity at the same site, can alter viral pathogenicity and immune recognition. Glycoproteomics provides a global view of viral glycan structures, revealing heterogeneity across strains or infection stages and highlighting glycan changes closely associated with immune evasion or antigenic drift. These insights offer valuable guidance for vaccine development by ensuring antigens closely mimic the native viral structure.
2. Phosphorylation
Phosphorylation acts as a molecular switch by altering protein charge and conformation, regulating viral processes throughout the life cycle. The phosphorylation state of viral polymerase complexes directly influences RNA synthesis efficiency and fidelity, determining whether early infection favors transcription or large-scale replication. Phosphorylation of nucleocapsid proteins modulates their RNA binding affinity and assembly, thereby affecting viral particle formation. Changes at specific phosphorylation sites also dictate protein subcellular localization, enabling shuttling between the nucleus and cytoplasm to facilitate genome replication and encapsidation. During infection, viruses manipulate host kinases to reprogram signaling networks, suppress antiviral responses, and restart the cell cycle to favor replication. Phosphoproteomics systematically tracks these dynamic events, clarifying how site-specific modifications drive infection timing and identifying kinase targets critical for viral dependence.
3. Ubiquitination
Ubiquitination is a PTM that attaches ubiquitin molecules to proteins to regulate their stability, signaling, and complex assembly, playing a central role in viral infection. K48-linked ubiquitination typically marks proteins for degradation, which viruses exploit to eliminate host antiviral factors and dampen interferon signaling. K63-linked ubiquitination often supports signaling or complex formation, helping viruses stabilize replication complexes and increase budding efficiency. Viruses also reverse these labels through deubiquitination to maintain protein stability. By fine-tuning the ubiquitination network, viruses balance their protein synthesis and turnover while disrupting host immune surveillance. Ubiquitinomics reveals which host and viral proteins undergo ubiquitination at different infection stages and identifies the E3 ligases or deubiquitinases acting as central regulatory nodes. This provides mechanistic evidence of how viruses hijack protein degradation systems and suggests novel antiviral targets.
4. Lipidation (Myristoylation & Palmitoylation)
Lipidation anchors viral proteins to membranes, which is essential for particle assembly and transmission. N-myristoylation typically occurs at the N-terminus of structural proteins, stably targeting them to the plasma membrane as assembly platforms. S-palmitoylation, a reversible modification, switches on or off depending on the infection stage, flexibly controlling membrane fusion, budding, and curvature. Loss of lipidation often prevents viruses from effectively associating with membranes, severely reducing infectivity and spread. Lipidation also reshapes host membrane microdomains, driving lipid raft clustering that facilitates assembly. Lipidomics-based PTM studies identify lipidation sites across the viral proteome, reveal their precise functions in assembly and release, and evaluate host lipid transferases as antiviral intervention targets. These findings emphasize lipidation as a critical regulator of viral spatial organization during the life cycle.
Virus Post-Translational Modifications Research at MtoZ Biolabs
In advancing our understanding of viral protein PTMs, systematic omics analyses are indispensable. MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider, provides advanced proteomics,metabolomics, and biopharmaceutical analysis services to researchers in biochemistry, biotechnology, and biopharmaceutical fields. We provide specialized viral proteomics services covering glycoproteomics, phosphoproteomics, ubiquitinomics, and lipidomics, enabling comprehensive profiling of viral PTMs at different stages of infection. With state-of-the-art high-resolution MS platforms (including Orbitrap Fusion Lumos and Q Exactive HF) and optimized sample preparation and enrichment workflows, MtoZ Biolabs performs precise PTM site identification, quantification, classification, distribution mapping, and dynamic analysis. Our team has extensive expertise in virology and proteomics, offering customized experimental design and data interpretation tailored to research goals. These services help researchers uncover how viruses exploit host PTM systems throughout their life cycles and support antiviral drug discovery, vaccine optimization, and biomarker development.
Contact us today, and MtoZ Biolabs will provide comprehensive proteomics support for your viral research and translational applications.