Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 107, Issue 3

Multiple origins and functions: evolutionary pathways of HSP70 proteins in viruses Open Access

Abstract

Heat shock protein 70s (HSP70s) are highly conserved molecular chaperones found across all domains of life, where they play essential roles in cellular stress responses. Whilst HSP70 homologues have been previously identified in closteroviruses that have ssRNA genomes, their broader presence and evolutionary history in viruses remain poorly understood. In this study, we conducted a comprehensive search of viral protein databases and identified HSP70 homologues in viruses beyond those with ssRNA genomes, including examples with dsDNA genomes in the class . These viral HSP70s exhibit diverse gene organizations, copy numbers and structural features. Notably, HSP70s of viruses from showed up to three gene copies per genome and distinct structural motifs, whilst those from closteroviruses displayed higher sequence and structural diversity, suggesting faster evolutionary rates. Structural and phylogenetic analyses revealed two major clusters of viral HSP70s, with dsDNA virus HSP70s closely resembling those of their protist hosts, supporting the hypothesis of horizontal gene transfer. In contrast, ssRNA virus HSP70s formed a distinct, highly divergent group. Our findings suggest multiple independent acquisitions of HSP70 genes by viruses and provide new insights into their evolutionary trajectories and potential functional adaptations.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): gene transfer , heat shock protein 70 superfamily and viruses
Funding
This study was supported by the:
  • MCIU/AEI/10.13039/501100011033 (Award PID2022-136912NB-I00)
    • Principal Award Recipient: SantiagoF. Elena
  • Generalitat Valenciana (Award ERDF a way of making Europe)
    • Principal Award Recipient: SantiagoF. Elena
  • Generalitat Valenciana (Award CIPROM/2022/59)
    • Principal Award Recipient: SantiagoF. Elena
© 2026 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.002242
2026-03-10
2026-04-11

Metrics

Loading full text...

Full text loading...

/deliver/fulltext/jgv/107/3/jgv002242.html?itemId=/content/journal/jgv/10.1099/jgv.0.002242&mimeType=html&fmt=ahah

References

  1. Hu C, Yang J, Qi Z, Wu H, Wang B et al. Heat shock proteins: biological functions, pathological roles, and therapeutic opportunities. MedComm 2022; 3:e161 [View Article]
     [Google Scholar]
  2. Rosenzweig R, Nillegoda NB, Mayer MP, Bukau B. The Hsp70 chaperone network. Nat Rev Mol Cell Biol 2019; 20:665–680 [View Article] [PubMed]
     [Google Scholar]
  3. Zhang Y, Zuiderweg ERP. The 70-kDa heat shock protein chaperone nucleotide-binding domain in solution unveiled as a molecular machine that can reorient its functional subdomains. Proc Natl Acad Sci USA 2004; 101:10272–10277 [View Article] [PubMed]
     [Google Scholar]
  4. Fernández-Fernández MR, Gragera M, Ochoa-Ibarrola L, Quintana-Gallardo L, Valpuesta JM. Hsp70 - a master regulator in protein degradation. FEBS Lett 2017; 591:2648–2660 [View Article] [PubMed]
     [Google Scholar]
  5. Easton DP, Kaneko Y, Subjeck JR. The Hsp110 and Grp170 stress proteins: newly recognized relatives of the Hsp70s. Cell Stress Chaper 2000; 5:276 [View Article]
     [Google Scholar]
  6. Raviol H, Sadlish H, Rodriguez F, Mayer MP, Bukau B. Chaperone network in the yeast cytosol: Hsp110 is revealed as an Hsp70 nucleotide exchange factor. EMBO J 2006; 25:2510–2518 [View Article] [PubMed]
     [Google Scholar]
  7. Tittelmeier J, Sandhof CA, Ries HM, Druffel-Augustin S, Mogk A et al. The HSP110/HSP70 disaggregation system generates spreading-competent toxic α-synuclein species. EMBO J 2020; 39:e103954 [View Article] [PubMed]
     [Google Scholar]
  8. Wang Z, Li Y, Yang X, Zhao J, Cheng Y et al. Mechanism and complex roles of HSC70 in viral infections. Front Microbiol 2020; 11:1577 [View Article]
     [Google Scholar]
  9. Chuang C-K, Yang T-H, Chen T-H, Yang C-F, Chen W-J. Heat shock cognate protein 70 isoform D is required for clathrin-dependent endocytosis of Japanese encephalitis virus in C6/36 cells. J Gen Virol 2015; 96:793–803 [View Article] [PubMed]
     [Google Scholar]
  10. Ravindran MS, Bagchi P, Inoue T, Tsai B. A non-enveloped virus hijacks host disaggregation machinery to translocate across the endoplasmic reticulum membrane. PLoS Pathog 2015; 11:e1005086 [View Article] [PubMed]
     [Google Scholar]
  11. Naito T, Momose F, Kawaguchi A, Nagata K. Involvement of Hsp90 in assembly and nuclear import of influenza virus RNA polymerase subunits. J Virol 2007; 81:1339–1349 [View Article] [PubMed]
     [Google Scholar]
  12. Gurer C, Höglund A, Höglund S, Luban J. ATPγS disrupts human immunodeficiency virus type 1 virion core integrity. J Virol 2005; 79:5557–5567 [View Article]
     [Google Scholar]
  13. Agranovsky AA, Boyko VP, Karasev AV, Koonin EV, Dolja VV. Putative 65 kDa protein of beet yellows closterovirus is a homologue of HSP70 heat shock proteins. J Mol Biol 1991; 217:603–610 [View Article] [PubMed]
     [Google Scholar]
  14. Dolja VV, Karasev AV, Koonin EV. Molecular biology and evolution of closteroviruses: sophisticated build-up of large RNA genomes. Annu Rev Phytopathol 1994; 32:261–285 [View Article]
     [Google Scholar]
  15. Peremyslov VV, Hagiwara Y, Dolja VV. HSP70 homolog functions in cell-to-cell movement of a plant virus. Proc Natl Acad Sci USA 1999; 96:14771–14776 [View Article]
     [Google Scholar]
  16. Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22:1658–1659 [View Article]
     [Google Scholar]
  17. Camacho C, Madded T, Tao T, Agarwala R, Morgulis A et al. BLAST+: architecture and applications. BMC Bioinformatics 2013; 41:W29–33
     [Google Scholar]
  18. Muhire BM, Varsani A, Martin DP. SDT: a virus classification tool based on pairwise sequence alignment and identity calculation. PLoS One 2014; 9:e108277 [View Article]
     [Google Scholar]
  19. Abramson J, Adler J, Dunger J, Evans R, Green T et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 2024; 630:493–500 [View Article]
     [Google Scholar]
  20. Holm L. Dali server: structural unification of protein families. Nucleic Acids Research 2022; 50:W210–W215 [View Article]
     [Google Scholar]
  21. DeLano WL. Pymol: an open-source molecular graphics tool. CCP4 Newsl Protein Crystallogr 2002; 40:82–92
     [Google Scholar]
  22. Holm L, Laiho A, Törönen P, Salgado M. DALI shines a light on remote homologs: one hundred discoveries. Protein Sci 2023; 32:e4519 [View Article] [PubMed]
     [Google Scholar]
  23. Bailey TL, Elkan C. Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 1994; 2:28–36 [View Article] [PubMed]
     [Google Scholar]
  24. Edgar RC. Muscle5: High-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny. Nat Commun 2022; 13:6968 [View Article] [PubMed]
     [Google Scholar]
  25. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol 2020; 37:1530–1534 [View Article] [PubMed]
     [Google Scholar]
  26. Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods 2017; 14:587–589 [View Article] [PubMed]
     [Google Scholar]
  27. Kozlov AM, Darriba D, Flouri T, Morel B, Stamatakis A. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 2019; 35:4453–4455 [View Article] [PubMed]
     [Google Scholar]
  28. Oberg N, Zallot R, Gerlt JA. EFI-EST, EFI-GNT, and EFI-CGFP: Enzyme Function Initiative (EFI) web resource for genomic enzymology tools. J Mol Biol 2023; 435:168018 [View Article] [PubMed]
     [Google Scholar]
  29. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13:2498–2504 [View Article] [PubMed]
     [Google Scholar]
  30. Satyanarayana T, Gowda S, Ayllón MA, Dawson WO. Closterovirus bipolar virion: evidence for initiation of assembly by minor coat protein and its restriction to the genomic RNA 5’ region. Proc Natl Acad Sci USA 2004; 101:799–804 [View Article] [PubMed]
     [Google Scholar]
  31. Kovacs GR, Guarino LA, Graham BL, Summers MD. Identification of spliced baculovirus RNAs expressed late in infection. Virology 1991; 185:633–643 [View Article] [PubMed]
     [Google Scholar]
  32. Dubois J, Terrier O, Rosa-Calatrava M. Influenza viruses and mRNA splicing: doing more with less. mBio 2014; 5:e00070–14 [View Article] [PubMed]
     [Google Scholar]
  33. Bouton C, Geldreich A, Ramel L, Ryabova LA, Dimitrova M et al. Cauliflower mosaic virus transcriptome reveals a complex alternative splicing pattern. PLoS One 2015; 10:e0132665 [View Article] [PubMed]
     [Google Scholar]
  34. Price AM, Steinbock RT, Lauman R, Charman M, Hayer KE et al. Novel viral splicing events and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts. PLoS Pathog 2022; 18:e1010797 [View Article] [PubMed]
     [Google Scholar]
  35. Duffy S, Shackelton LA, Holmes EC. Rates of evolutionary change in viruses: patterns and determinants. Nat Rev Genet 2008; 9:267–276 [View Article] [PubMed]
     [Google Scholar]
  36. Dolja VV, Kreuze JF, Valkonen JPT. Comparative and functional genomics of closteroviruses. Virus Research 2006; 117:38–51 [View Article]
     [Google Scholar]
  37. Alzhanova DV, Napuli AJ, Creamer R, Dolja VV. Cell-to-cell movement and assembly of a plant closterovirus: roles for the capsid proteins and Hsp70 homolog. EMBO J 2001; 20:6997–7007 [View Article]
     [Google Scholar]
  38. Zhang X, Yu W. Heat shock proteins and viral infection. Front Immunol 2022; 13:947789 [View Article]
     [Google Scholar]
/content/journal/jgv/10.1099/jgv.0.002242
Loading
Multiple origins and functions: evolutionary pathways of HSP70 proteins in viruses
J. Gen. Virol. 107, 002242 (2026); https://doi.org/10.1099/jgv.0.002242
/content/journal/jgv/10.1099/jgv.0.002242
/content/journal/jgv/10.1099/jgv.0.002242
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An error occurred
Approval was partially successful, following selected items could not be processed due to error