Protein Acetylation Going Viral: Implications in Antiviral Immunity and Viral Infection

Abstract

During viral infection, both host and viral proteins undergo post-translational modifications (PTMs), including phosphorylation, ubiquitination, methylation, and acetylation, which play critical roles in viral replication, pathogenesis, and host antiviral responses. Protein acetylation is one of the most important PTMs and is catalyzed by a series of acetyltransferases that divert acetyl groups from acetylated molecules to specific amino acid residues of substrates, affecting chromatin structure, transcription, and signal transduction, thereby participating in the cell cycle as well as in metabolic and other cellular processes. Acetylation of host and viral proteins has emerging roles in the processes of virus adsorption, invasion, synthesis, assembly, and release as well as in host antiviral responses. Methods to study protein acetylation have been gradually optimized in recent decades, providing new opportunities to investigate acetylation during viral infection. This review summarizes the classification of protein acetylation and the standard methods used to map this modification, with an emphasis on viral and host protein acetylation during viral infection.

Keywords: acetylation; acetyltransferases; antiviral immunity; deacetylases; viral infection.

Figure 1

Acetylation modulates key factors of type Ⅰ interferon (IFN) pathway during viral infection. In the upstream IFN signaling pathway, molecules such as cGAS, RIG-I, MAVS, IRF3, IRF7, and NF-κB, can be acetylated or deacetylated by specific acetyltransferases or deacetylases, modulating the production of IFN. In the downstream IFN signaling pathway, CBP can acetylate IFNAR2, STAT1, and STAT2, facilitating transcriptional activation of interferon-stimulated genes.

Figure 2

Effect of acetylation of viral proteins during viral infection. Representative acetylation of viral proteins and their function during virus–host interaction. The 3-D structures for the viral proteins were retrieved from the PDB database (PDB accession numbers 2NNU, 6IWD, 7K0W, 6U28, 2IQH, 7JM3, 3LPU, 1JFW, 1SSK, 6WZO, 7JZJ, and 5Z9W). The acetylation chains are representative of hypothetical schematics.