Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

Abstract

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

Impact of Ribosome Activity on SARS-CoV-2 LNP – Based mRNA Vaccines

“…Complete SARS-CoV-2 mRNA strand fragment translation leads to S protein neutralizing antibody (nAb) multiple copies production, motivating human immune system to respond protectively against the SARS-CoV-2 infection by sensitizing specific CD4 and CD8 T cells for exposing a high immunogenic activity (Wang et al, 2020). It is also important to be mentioned that host cellmediated post-translational modifications (PTMs)-including predominantly glycosylation and phosporylation-are crucial for the final proteins' functionality in viral infections (Kumar et al, 2020a). Especially, in SARS-CoV-2 RNA cell entry, differentially expressed human glycogens have been recently detected (Oommen et al, 2021).…”

Target Discovery for Host-Directed Antiviral Therapies: Application of Proteomics Approaches

“…High-throughput characterization of posttranslational modifications (PTMs) especially offer valuable insight into the biology of viral infections, as PTMs have critical roles in many different aspects of infection that have both proviral (inhibiting interferon response or promoting viral replication and assembly) and antiviral consequences (degrading viral proteins through ubiquitination or inactivating them through changes in PTMs) ( 55 , 56 ). Various studies also revealed how the dynamic interplay between different PTMs (such as phosphorylation, ubiquitination, and SUMOylation) regulates processes like pathogen-sensing pathways and innate immune signaling, underscoring the importance of characterizing the dynamics of these modifications upon infection ( 57 – 60 ).…”

The Putative Roles and Functions of Indel, Repetition and Duplication Events in Alphavirus Non-Structural Protein 3 Hypervariable Domain (nsP3 HVD) in Evolution, Viability and Re-Emergence

“…Interestingly, nsP3 is the only protein which can be phosphorylated among all alphavirus replicase proteins. The nsP3 HVD is heavily phosphorylated and is involved in signaling cascades, alphavirus RC formation, and alphavirus virulent phenotypes [176,177]. Structural studies on nsP3 HVD are key to gaining insight into alphavirus RC assembly and functions during viral replication at the molecular level.…”