Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Activation of heat-shock response by an adenovirus is essential for virus replication

Nature volume 407, pages 207–211 (2000)Cite this article

Abstract

Successful viral infection requires viruses to redirect host biochemistry to replicate the viral genome, and produce and assemble progeny virions. Cellular heat-shock responses, which are characterized as elevation and relocalization of heat-shock proteins, occur during replication of many viruses1,2,3,4,5,6,7. Such responses might be host reactions to the synthesis of foreign protein, or might be irrelevant consequences of the viral need to activate transcription. Alternatively, as heat-shock proteins can facilitate protein folding8,9, activating a heat-shock response might be a specific virus function ensuring proper synthesis of viral proteins and virions. It is not possible to determine whether heat-shock response is essential for virus replication, because the implicated viral genes (such as Ad5 E1A, ref. 10) also control other essential replication steps. Here we report that expression of Gam1, a protein encoded by the avian virus CELO (ref. 11), elevates and relocalizes hsp70 and hsp40. Gam1-negative CELO is replication-defective; however, Gam1 function can be partially replaced by either heat shock or forced hsp40 expression. Thus, an essential function of Gam1 during virus replication is to activate host heat-shock responses with hsp40 as a primary target.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Gam1 expression elevates heat-shock protein levels.
Figure 2: hsp40 and hsp70 are upregulated by Gam1 expressed from a transfected plasmid.
Figure 3: Gam1 relocates hsp40 and hsp70 to the nucleus.
Figure 4: hsp40 and hsp70 are upregulated during CELO infection.
Figure 5: Gam1 is required for CELO replication and can be replaced by heat shock or hsp40.

Similar content being viewed by others

References

  1. Nevins, J. R. Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell 29, 913–919 (1982).

    Article  CAS  PubMed  Google Scholar 

  2. Kao, H. T. & Nevins, J. R. Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Mol. Cell. Biol. 3, 2058– 2065 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Phillips, B., Abravaya, K. & Morimoto, R. I. Analysis of the specificity and mechanism of transcriptional activation of the human hsp70 gene during infection by DNA viruses. J. Virol. 65, 5680–5692 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Santomenna, L. D. & Colberg-Poley, A. M. Induction of cellular hsp70 expression by human cytomegalovirus. J. Virol. 64, 2033–2040 ( 1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Ohgitani, E., Kobayashi, K., Takeshita, K. & Imanishi, J. Biphasic translocation of a 70 kDa heat shock protein in human cytomegalovirus-infected cells. J. Gen. Virol. 80, 63– 68 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Kobayashi, K. et al. Herpes simplex virus-induced expression of 70 kDa heat shock protein (HSP70) requires early protein synthesis but not viral DNA replication. Microbiol. Immunol. 38, 321– 325 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. Collins, P. L. & Hightower, L. E. Newcastle disease virus stimulates the cellular accumulation of stress (heat shock) mRNAs and proteins. J. Virol. 44, 703–707 ( 1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Mayer, M. P. & Bukau, B. HSP70 chaperone systems: diversity of cellular functions and mechanism of action. Biol. Chem. 379, 261–268 (1998).

    CAS  PubMed  Google Scholar 

  9. Kelley, W. L. Molecular chaperones: How J domains turn on Hsp70s. Curr. Biol. 9, R305–308 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  10. Flint, J. & Shenk, T. Viral transactivating proteins. Annu. Rev. Genet. 31, 177–212 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Chiocca, S., Baker, A. & Cotten, M. Identification of a novel anti-apoptotic protein, GAM-1, encoded by the CELO adenovirus. J. Virol. 71, 3168–3177 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Gabai, V. L. et al. Hsp70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance. J. Biol. Chem. 272, 18033–18037 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. Mosser, D. D. et al. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol. Cell. Biol. 17, 5317–5327 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Welch, W. J. & Feramisco, J. R. Nuclear and nucleolar localization of the 72,000-dalton heat shock protein in heat-shocked mammalian cells. J. Biol. Chem. 259, 4501–4513 (1984)

    CAS  PubMed  Google Scholar 

  15. Hattori, H. et al. Intracellular localization and partial amino acid sequence of a stress-inducible 40-kDa protein in HeLa cells. Cell. Struct. Funct. 17, 77–86 ( 1992).

    Article  CAS  PubMed  Google Scholar 

  16. Polissi, A., Goffin, L. & Georgopoulos, C. The Escherichia coli heat shock response and bacteriophage lambda development. FEMS Microbiol. Rev. 17, 159–169 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Liu, J. S. et al. Human Hsp70 and Hsp40 chaperone proteins facilitate human papillomavirus-11 E1 protein binding to the origin and stimulate cell-free DNA replication. J. Biol. Chem. 273, 30704 –30712 (1998).

    Article  CAS  PubMed  Google Scholar 

  18. Campbell, K. S. et al. DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA replication. Genes Dev. 11, 1098–1110 (1997).

    Article  CAS  PubMed  Google Scholar 

  19. Kelley, W. L. & Georgopoulos, C. The T/t common exon of simian virus 40, JC, and BK polyomavirus T antigens can functionally replace the J-domain of the Escherichia coli DnaJ molecular chaperone. Proc. Natl Acad. Sci. USA 94, 3679– 3684 (1997).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  20. Stubdal, H. et al. Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen. Mol. Cell. Biol. 17, 4979–4990 ( 1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Srinivasan, A. et al. The amino-terminal transforming region of simian virus 40 large T and small t antigens functions as a J domain. Mol. Cell. Biol. 17, 4761–4773 ( 1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chiocca, S. et al. The complete DNA sequence and genomic organization of the avian adenovirus CELO. J. Virol. 70, 2939 –2949 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Chartier, C. et al. Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli. J. Virol. 70, 4805–4810 ( 1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Michou, A. -I., Lehrmann, H., Saltik, M. & Cotten, M. Mutational analysis of the avian adenovirus CELO, which provides a basis for gene delivery vectors. J. Virol. 73, 1399–1410 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Ohtsuka, K. Cloning of a cDNA for heat-shock protein hsp40, a human homologue of bacterial DnaJ. Biochem. Biophys. Res. Commun. 197, 235–240 (1993).

    Article  CAS  PubMed  Google Scholar 

  26. Hunt, C. & Morimoto, R. I. Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc. Natl Acad. Sci. USA 82, 6455– 6459 (1985).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stratford-Perricaudet, L. D., Makeh, I., Perricaudet, M. & Briand, P. Widespread long-term gene transfer to mouse skeletal muscles and heart. J. Clin. Invest. 90, 626–630 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Evan, G. I., Lewis, G. K., Ramsay, G. & Bishop, J. M. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol. Cell. Biol. 5, 3610–3616 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kawaguchi T., Nomura, K., Hirayama, Y. & Kitagawa, T. Establishment and characterization of a chicken hepatocellular carcinoma cell line, LMH. Cancer Res. 47, 4460–4464 (1987).

    PubMed  Google Scholar 

  30. Graham F. L., Smiley, J., Russell, W. C. & Nairn, R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. 36, 59– 74 (1977).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M. Raff for suggesting the heat-shock complementation and G. Christofori for his comments on the manuscript. We thank K. Ohtsuka for the hsp40 cDNA and S. Fox and R. Morimoto for the hsp70 gene.

Author information

Authors and Affiliations

  1. Institute for Molecular Pathology , Dr Bohr-Gasse 7, Vienna, A-1030, Austria

    Jolanta B. Glotzer, Mediyha Saltik, Anne-Isabelle Michou & Matt Cotten

  2. Department of Experimental Oncology, European Institute of Oncology, Milan, 20141, Italy

    Susanna Chiocca

  3. Department of Medicine, The University of New Mexico, Albuquerque, 87131-5271 , New Mexico, USA

    Pope Moseley

Authors
  1. Jolanta B. Glotzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mediyha Saltik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susanna Chiocca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anne-Isabelle Michou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pope Moseley
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matt Cotten
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matt Cotten.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Glotzer, J., Saltik, M., Chiocca, S. et al. Activation of heat-shock response by an adenovirus is essential for virus replication. Nature 407, 207–211 (2000). https://doi.org/10.1038/35025102

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35025102

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing