# The roles of post-translational modifications in the pathogenesis of RNA viruses: allies or adversaries?

**Authors:** Tong Shao, Zhichao Pei, Yuting Wang, Yitong Zhao, Huimin Fan, Jiahui Pan

PMC · DOI: 10.3389/fmicb.2026.1768721 · Frontiers in Microbiology · 2026-02-12

## TL;DR

This paper reviews how viruses use protein modifications to control infections and suggests these modifications could be targets for new antiviral treatments.

## Contribution

The paper integrates recent proteomics findings to explore 10 PTM types in RNA virus infections, highlighting their roles and therapeutic potential.

## Key findings

- Viruses exploit host post-translational modifications (PTMs) to reprogram cellular metabolism and signaling.
- Ten major PTM types are shown to have multifaceted roles across the RNA virus life cycle.
- PTMs are identified as potential targets for developing antiviral strategies and treating virus-related diseases.

## Abstract

Infectious diseases continue to pose major threats to global public health, owing to the persistent emergence of novel and re-emerging viruses. However, the intricate mechanisms governing virus–host interactions remain incompletely understood. Precise regulation of protein function is critical during viral infection, and post-translational modifications (PTMs), as key modulators of protein activity, are extensively exploited by viruses at all stages of their life cycle. Upon entry into host cells, viruses frequently hijack host PTMs to reprogram cellular metabolism and signaling, thereby shaping infection outcomes. This review highlights recent advances in 10 major PTM types implicated in RNA virus infections, emphasizing their multifaceted roles across the viral life cycle. By integrating the latest proteomics findings, it aims to provide deeper insight into PTMs as potential targets for antiviral strategies and to explore their promise in treating virus-associated diseases.

## Full-text entities

- **Genes:** M (membrane glycoprotein) [NCBI Gene 43740571], ORF8 (ORF8 protein) [NCBI Gene 43740577], ERVK-20 (endogenous retrovirus group K member 20) [NCBI Gene 100616444] {aka c11_B, env}, RETREG1 (reticulophagy regulator 1) [NCBI Gene 54463] {aka FAM134B, JK-1, JK1}, ZDHHC5 (zDHHC palmitoyltransferase 5) [NCBI Gene 25921] {aka DHHC5, ZNF375}, EIF2A (eukaryotic translation initiation factor 2A) [NCBI Gene 83939] {aka CDA02, EIF-2A, MST089, MSTP004, MSTP089}, GOLGA7 (golgin A7) [NCBI Gene 51125] {aka GCP16, GOLGA3AP1, GOLGA7A, HSPC041}, RNF130 (ring finger protein 130) [NCBI Gene 55819] {aka G1RP, G1RZFP, GOLIATH, GP}, KPNA5 (karyopherin subunit alpha 5) [NCBI Gene 3841] {aka IPOA6, SRP6}, APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic subunit 3G) [NCBI Gene 60489] {aka A3G, ARCD, ARP-9, ARP9, CEM-15, CEM15}, HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320] {aka EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N}, ORF7a (ORF7a protein) [NCBI Gene 43740573], SRSF1 (serine and arginine rich splicing factor 1) [NCBI Gene 6426] {aka ASF, NEDFBA, SF2, SF2p33, SFRS1, SRp30a}, PTPA (protein phosphatase 2 phosphatase activator) [NCBI Gene 5524] {aka PARK25, PP2A, PPP2R4, PR53}, TAT (tyrosine aminotransferase) [NCBI Gene 6898], BCL2L1 (BCL2 like 1) [NCBI Gene 598] {aka BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52}, gag (Pr55(Gag)) [NCBI Gene 155030], STAT2 (signal transducer and activator of transcription 2) [NCBI Gene 6773] {aka IMD44, ISGF-3, P113, PTORCH3, STAT113}, ORF6 (ORF6 protein) [NCBI Gene 43740572], IL17RB (interleukin 17 receptor B) [NCBI Gene 55540] {aka CRL4, EVI27, IL17BR, IL17RH1}, E (envelope protein) [NCBI Gene 43740570], KAT2A (lysine acetyltransferase 2A) [NCBI Gene 2648] {aka GCN5, GCN5L2, PCAF-b, hGCN5}, TRIM21 (tripartite motif containing 21) [NCBI Gene 6737] {aka RNF81, RO52, Ro/SSA, SSA, SSA1, TRIM21/Ro52}, ORF1ab (ORF1a polyprotein;ORF1ab polyprotein) [NCBI Gene 43740578], NMT1 (N-myristoyltransferase 1) [NCBI Gene 4836] {aka HsNMT1, NMT}, N (nucleocapsid phosphoprotein) [NCBI Gene 43740575], TRIM6 (tripartite motif containing 6) [NCBI Gene 117854] {aka RNF89}, DNER (delta/notch like EGF repeat containing) [NCBI Gene 92737] {aka UNQ26, bet}, WWP2 (WW domain containing E3 ubiquitin protein ligase 2) [NCBI Gene 11060] {aka AIP2, WWp2-like}, AMFR (autocrine motility factor receptor) [NCBI Gene 267] {aka GP78, RNF45, SPG89}, KAT2B (lysine acetyltransferase 2B) [NCBI Gene 8850] {aka CAF, P/CAF, PCAF}, OTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) [NCBI Gene 55611] {aka HSPC263, OTB1, OTU1}, COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, CNOT4 (CCR4-NOT transcription complex subunit 4) [NCBI Gene 4850] {aka CLONE243, NOT4, NOT4H}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, NEU1 (neuraminidase 1) [NCBI Gene 4758] {aka NANH, NEU, SIAL1}, TMBIM4 (transmembrane BAX inhibitor motif containing 4) [NCBI Gene 51643] {aka CGI-119, GAAP, LFG4, S1R, ZPRO}, PIN1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) [NCBI Gene 5300] {aka DOD, UBL5}, DDX21 (DExD-box helicase 21) [NCBI Gene 9188] {aka GUA, GURDB, II/Gu, RH, RH II/Gu, RH-II/GU}, USP29 (ubiquitin specific peptidase 29) [NCBI Gene 57663] {aka HOM-TES-84/86}, DDIT3 (DNA damage inducible transcript 3) [NCBI Gene 1649] {aka AltDDIT3, C/EBPzeta, CEBPZ, CHOP, CHOP-10, CHOP10}, CUL5 (cullin 5) [NCBI Gene 8065] {aka CUL-5, VACM-1, VACM1}, TOMM70 (translocase of outer mitochondrial membrane 70) [NCBI Gene 9868] {aka TOMM70A, Tom70}, NEDD8 (NEDD8 ubiquitin like modifier) [NCBI Gene 4738] {aka NEDD-8}, CD209 (CD209 molecule) [NCBI Gene 30835] {aka CDSIGN, CLEC4L, DC-SIGN, DC-SIGN1, hDC-SIGN}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BRD4 (bromodomain containing 4) [NCBI Gene 23476] {aka CAP, CDLS6, FSHRG4, HUNK1, HUNKI, MCAP}, PPIA (peptidylprolyl isomerase A) [NCBI Gene 5478] {aka CYPA, CYPH, HEL-S-69p}, EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3) [NCBI Gene 9451] {aka PEK, PERK, WRS}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, ZDHHC11 (zDHHC palmitoyltransferase 11) [NCBI Gene 79844] {aka ZNF399}, Nef [NCBI Gene 156110], SPECC1 (sperm antigen with calponin homology and coiled-coil domains 1) [NCBI Gene 92521] {aka CYTSB, HCMOGT-1, HCMOGT1, NSP, NSP5}, OCA2 (OCA2 melanosomal transmembrane protein) [NCBI Gene 4948] {aka BEY, BEY1, BEY2, BOCA, D15S12, EYCL}, SMR3A (submaxillary gland androgen regulated protein 3A) [NCBI Gene 26952] {aka P-B1, PBI, PRL5, PROL5}, ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636] {aka G1P2, IFI15, IMD38, IP17, UCRP, hUCRP}, NMT2 (N-myristoyltransferase 2) [NCBI Gene 9397]
- **Diseases:** Infectious diseases (MESH:D003141), viral (MESH:D014777), toxicity (MESH:D064420), TS (MESH:D005879), infection (MESH:D007239), arenavirus infections (MESH:D001117), SARS-CoV-2 (MESH:D000086382), IAV infection (MESH:D007251), RNA virus infection (MESH:D012327)
- **Chemicals:** palmitic acid (MESH:D019308), lipid (MESH:D008055), cysteine (MESH:D003545), ATP (MESH:D000255), calcium (MESH:D002118), lysine (MESH:D008239), myristic acid (MESH:D019814), PO4 (-), S (MESH:D013455), succinyl-CoA (MESH:C012046), amino acid (MESH:D000596), DDD85646 (MESH:C549249), sialic acid (MESH:D019158), ADP (MESH:D000244), glycan (MESH:D011134)
- **Species:** Mopeia virus [taxon 11629], Dengue virus (no rank) [taxon 12637], HF [taxon 2008765], Human coronavirus NL63 (no rank) [taxon 277944], Lassa virus [taxon 11620], West Nile virus (no rank) [taxon 11082], flavivirus [taxon 11051], Mason-Pfizer monkey virus (no rank) [taxon 11855], Vesicular stomatitis virus (species) [taxon 11276], Rotavirus (genus) [taxon 10912], Influenza A virus (no rank) [taxon 11320], Severe fever with thrombocytopenia syndrome virus (no rank) [taxon 1003835], Rift Valley fever virus (no rank) [taxon 11588], Homo sapiens (human, species) [taxon 9606], Gammacoronavirus (genus) [taxon 694013], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Filoviridae (family) [taxon 11266], Marburg virus [taxon 186537], Pseudovirus (genus) [taxon 186672], human metapneumovirus (no rank) [taxon 162145], Enterovirus A71 (no rank) [taxon 39054], Human immunodeficiency virus 1 (no rank) [taxon 11676], Lyssavirus rabies (species) [taxon 11292], hepatitis C virus [taxon 11103], Ebola virus (no rank) [taxon 1570291], Zika virus (no rank) [taxon 64320], Japanese encephalitis virus (no rank) [taxon 11072], Aedes aegypti (yellow fever mosquito, species) [taxon 7159], Sindbis virus (no rank) [taxon 11034], Ebola virus [taxon 186536], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** lysine residue 119, S181E, S181, D614G
- **Cell lines:** HT29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), MA104 — Chlorocebus pygerythrus (Vervet monkey), Spontaneously immortalized cell line (CVCL_3845)

## Full text

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## Figures

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## References

137 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936031/full.md

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Source: https://tomesphere.com/paper/PMC12936031