Abstract
Acute infection of mammalian cells with several types of RNA and DNA viruses often results in induction of heat-shock gene expression. The presence of hsp70 in intact virions, as well as the transient association of HSP with viral proteins and assembly intermediates during virus replication, has also been reported in several experimental models. Moreover, a possible role of heat shock proteins in the beneficial effect of fever and local hyperthermia during acute virus infection has been hypothesized. However, the role of HSP in virus replication remains to be defined.
At the beginning of the 1980s, the use of virus models to investigate the molecular events that follow the exposure of mammalian cells to prostaglandins led to the serendipitous discovery that specific arachidonic acid derivatives are potent inhibitors of virus replication. This finding was rapidly followed by the observation that treatment of virus-infected cells with the antiviral prostaglandin A1 (PGA1) resulted in the accumulation of a 70 KDa cellular protein, which was identified as hsp70. It is now well established that cyclopentenone prostaglandins, which exert potent antiviral activity in several DNA and RNA virus models, induce hsp70 synthesis through cycloheximide-sensitive activation of heat shock transcription factor.
This chapter discusses the role of heat shock proteins in the control of virus replication and summarizes the results of our recent work, which indicate that hsp70 is actively involved in the antiviral activity of prostaglandins.
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Amici, C., Giorgi, C., Rossi, A., and Santoro, M. G., Selective inhibition of virus protein synthesis by prostaglandin A1: a translational block associated with HSP70 synthesis. J. Virol.68 (1994) 6890–6899.
Amici, C., Sistonen, L., Santoro, M. G., and Morimoto, R. I., Anti-proliferative prostaglandins activate heat shock transcription factor. Proc. natl Acad. Sci. USA89 (1992) 6227–6231.
Angelidis, C. E., Lazaridis, I., and Pagoulatos, G. N., Specific inhibition of simian virus 40 protein synthesis by heat and arsenite treatment. Eur. J. Biochem.172 (1988) 27–34.
Ankel, H., Mittnacht, S., and Jakobsen, H., Antiviral activity of prostaglandin A on encephalomyocarditis virus-infected cells: a unique effect unrelated to interferon. J. gen. Virol.66 (1985) 2355–2364.
Ankel, H., Turriziani, O., and Antonelli, G., Prostaglandin A inhibits replication of human immunodeficiency virus during acute infection. J. gen. Virol.72 (1991) 2797–2800.
Bader, T., and Ankel, H., Inhibition of primary transcription of vesicular stomatitis virus by prostaglandin A1. J. gen. Virol.71 (1990) 2823–2832.
Beckman, R. P., Mizzen, L. A., and Welch, W. J., Interaction of hsp70 with newly synthesized proteins: implications for protein folding and assembly. Science248 (1990) 850–854.
Benavente, J., Esteban, M., Jaffe, B. M., and Santoro, M. G., Selective inhibition of viral gene expression as the mechanism of the antiviral action of PGA1 in vaccinia virus-infected cells. J. gen. Virol.65 (1984) 599–608.
Bennett, I. L., and Nicastri, A., Fever as a mechanism of resistance. Bact. Rev.24 (1960) 16–34.
Bond, U., and Schlesinger, M. J., Heat-shock proteins and development. Adv. Genet.24 (1987) 1–29.
Braakman, I., Hoover-Litty, H., Wagner, K. R., and Helenius, A., Folding of influenza hemagglutinin in the endoplasmic reticulum. J. Cell Biol.114 (1991) 401–411.
Carvalho, M. G. C., and Fournier, M. V., Effect of heat shock on gene expression ofAedes albopictus cells infected with Mayaro virus. Res. Virol.142 (1991) 25–31.
Casjens, S., and Hendrix, R., Control mechanisms in dsDNA bacteriophage assembly, in: The Bacteriophages, vol. 1, pp. 15–91. Ed. R. Calendar. Plenum Press, New York 1988.
Cheung, R. K., and Dosch, H., The growth transformation of human B cells involves superinduction of hsp70 and hsp90. Virology193 (1993) 700–708.
Ciereszko, L. S., Gopichand, Y., Schmitz, F. J., Schneider, W. P., and Bundy, G. L., Prostaglandin (15S)-PGA2 derivatives in the gorgonian Plexaura homomalla (Esper), Forma Kukenthali Moser. Experientia41 (1985) 37–38.
Collins, P. L., and Hightower, L., Newcastle Disease Virus stimulates the cellular accumulation of stress (heat shock) proteins. J. Virol.44 (1982) 703–707.
Davis, T. W., Randall, R. E., and Lamb, R. A., Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78/BiP in the endoplasmic reticulum and extensive internalization from the cell surface. J. Cell Biol.109 (1989) 3273–3289.
De Marco, A., and Santoro, M. G., Antiviral effect of short hyperthermic treatment at specific stages of vesicular stomatitis virus replication cycle. J. gen. Virol. 74 (1993) 1685–1690.
Dinarello, C. A., and Wolff, S. M., Molecular basis of fever in humans. Am. J. Med.72 (1982) 799–819.
D'Onofrio, C., Alvino, E., Garaci, E., Bonmassar, E., and Santoro, M. G., Selection of HTLV-1 positive clones is prevented by prostaglandin A in infected cord blood cultures. Br. J. Cancer61 (1990) 207–214.
Friedman, D. I., Olson, E. R., Georgopoulos, C., Tilly, K., Herskowitz, I., and Banuett, F., Interactions of Bacteriophage and host macromolecules in the growth of bacteriophage λ. Microbiol. Rev.48 (1984) 299–325.
Galinski, M. S., Paramyxoviridae: transcription and replication. Adv. Virus Res.39 (1991) 129–162.
Garaci, E., Paoletti, R., and Santoro, M. G., Prostaglandins in Cancer Research. Springer, Berlin-Heidelberg 1987.
Garry, R. F., Emin, T. U., and Bose, H. R., Induction of stress proteins in Sindbis virus- and vesicular stomatitis virus-infected cells. Virology129 (1983) 319–332.
Gething, M., and Sambrook, J., Protein folding in the cell. Nature355 (1992) 33–45.
Hensold, J. O., Hunt, C. R., Calderwood, S. K., Housman, D. E., and Kingston, R. E., DNA binding of heat shock factor to the heat shock element is insufficient for transcriptional activation in murine erythroleukemia cells. Molec. cell. Biol.10 (1990) 1600–1608.
Hughes Fulford, M., McGrath, M. S., Hanks, D., Erickson, S., and Pulliam, L., Effects of dimethyl prostaglandin A1 on herpes simplex virus and immunodeficiency virus replication. Antimicrob. Agents Chemother.36 (1992) 2253–2258.
Jindal, S., and Young, R. A., Vaccinia virus infection induces a stress response that leads to association of Hsp70 with viral proteins. J. Virol.66 (1992) 5357–5362.
Kao, H., and Nevins, J. R., Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Molec. cell. Biol3 (1983) 2058–2065.
Kao, H., Capasso, O., Heintz, N., and Nevins, J. R., Cell cycle control of the human hsp70 gene: implications for the role of a cellular E1A-like function. Molec. cell. Biol.5 (1985) 628–633.
Khandjian, E. W., and Turler, H., Simian virus 40 and polyoma virus induce the synthesis of heat shock proteins in permissive cells. Molec. cell. Biol.3 (1983) 1–8.
Kluger, M. J., Is fever beneficial? Yale J. Biol. Med.59 (1986) 89–95.
La Thangue, N. B., Shriver, K., Dawson, C., and Chan, W. L., Herpes Simplex virus infection causes the accumulation of a heat shock protein. EMBO J.3 (1984) 267–277.
La Thangue, N. B., and Latchman, D. S., A cellular protein related to heat shock protein 90 accumulates during herpes simplex virus infection and is overexpressed in transformed cells. Expl Cell Res.178 (1988) 169–179.
Lindquist, S., and Craig, E. A., The heat-shock proteins. A. Rev. Genet.22 (1988) 631–677.
Lingappa, J. R., Martin, R. L., Wong, M. L., Ganem, D., Welch, W. J., and Lingappa, V. R., A eukaryotic cytosolic chaperonin is associated with a high molecular weight intermediate in the assembly of hepatitis B virus capsid, a multimeric particle. J. Cell Biol.125 (1994) 99–111.
Lwoff, A., Death and transfiguration of a problem. Bact. Rev.33 (1969) 390–403.
Macejak, D. G., and Luftig, R. B., Association of hsp70 with the adenovirus type 5 fiber protein in infected HEp-2 cells. Virology180 (1991) 120–125.
Macejak, D. G., and Sarnow, P., Association of heat shock protein 70 with enterovirus capsid precursor P1 in infected human cells. J. Virol.66 (1992) 1520–1527.
Mastromarino, P., Conti, C., Petruzziello, R., De Marco, A., Pica, F., and Santoro, M. G., Inhibition of Sindbis virus replication by cyclopentenone prostaglandins: a cell-mediated event associated with heat shock protein synthesis. Antiviral Res.20 (1993) 209–222.
Muñoz, A., Alonso, M. A., and Carrasco, L., Synthesis of heat shock proteins in HeLa cells: inhibition by virus infection. Virology137 (1984) 150–159.
Nevins, J. R., Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell29 (1982) 913–919.
Ninnemann, J. L., Prostaglandins, Leukotrienes and the Immune Response. Cambridge University Press, Cambridge, New York 1988.
Notarianni, E. L., and Preston, C. M., Activation of cellular stress protein genes by herpes simplex virus temperature-sensitive mutants which overproduce early polypeptides. Virology123 (1982) 113–122.
Nuss, D. L., and Koch, G., Differential inhibition of vesicular stomatitis virus polypeptide synthesis by hypertonic initiation block. J. Virol.17 (1976) 283–286.
Oglesbee, M., and Krakowka, S., Cellular stress response induces selective intranuclear trafficking and accumulation of morbillivirus major core protein. Lab. Invest.68 (1993) 109–117.
Panasiak, W., Oraczewska, A., and Luczak, M., Influence of hyperthermia on experimental viral infections in vitro, in: Consensus on Hyperthermia, pp. 471–475. Eds H. I. Bicher, J. R. McLaren and G. M. Pigliucci. Plenum Press, New York 1990.
Peluso, R. W., Lamb, R. A., and Choppin, P. W., Polypeptide synthesis in simian virus 5-infected cells. J. Virol.23 (1977) 177–187.
Peluso, R. W., Lamb, R. A., and Choppin, P. W., Infection with paramyxoviruses stimulates synthesis of cellular polypeptides that are also stimulated in cells transformed by Rous sarcoma virus or deprived of glucose. Proc. natl Acad. Sci. USA75 (1978) 6120–6124.
Phillips, B., Abravaya, K., and 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 (1991) 5680–5692.
Pica, F., De Marco, A., De Cesare, F., and Santoro, M. G., Inhibition of vesicular stomatitis virus replication by Δ12-prostaglandin J2 is regulated at two separate levels and is associated with induction of stress protein synthesis. Antiviral Res.20 (1993) 193–208.
Robert, A., Prostaglandins and the gastrointestinal tract, in: Physiology of the Gastrointestinal Tract, pp. 1407–1434. Ed. L. R. Johnson. Raven Press, New York 1981.
Rossi, A., and Santoro, M. G., Induction of a 32-kDa stress protein by prostaglandin A1 in cultured murine cells. Ann. N. Y. Acad. Sci.744 (1984) 326–329.
Russel, J., Stow, E. C., Stow, N. D., and Preston, C. M., Abnormal forms of the herpes simplex virus immediate early polypeptide Vmw 175 induce the cellular stress response. J. gen. Virol.68 (1987) 2397–2406.
Sagara, J., and Kawai, A., Identification of heat shock protein 70 in the rabies virion. Virology190 (1992) 845–848.
Samuelsson, B., Prostaglandins, thromboxanes and leukotrienes: biochemical pathways. in: Prostaglandins and Cancer: First International Conference, pp. 1–19. Eds T. J. Powles, R. S. Bochman, K. V. Honn and P. Ramwell Alan R. Liss Inc., New York 1982.
Santomenna, L. D., and Colberg-Poley, A. M., Induction of cellular hsp70 expression by human cytomegalovirus. J. Virol.64 (1990) 2033–2040.
Santoro, M. G., Involvement of protein synthesis in the antiproliferative and the antiviral action of prostaglandins. in: Prostaglandins in Cancer Research, pp. 97–114. Eds E. Garaci, R. Paoletti and M. G. Santoro. Springer, Berlin-Heidelberg 1987.
Santoro, M. G., Benedetto, A., Carruba, G., Garaci, E., and Jaffe, B. M., Prostaglandin A compounds as antiviral agents. Science209 (1980) 1032–1034.
Santoro, M. G., Jaffe, B. M., Elia, G., and Benedetto, A., Prostaglandin A1 induces the synthesis on a new protein in cultured AGMK cells. Biochem. biophys. Res. Commun.107 (1982) 1179–1184.
Santoro, M. G., Jaffe, B. M., Garaci, E., and Esteban, M., Antiviral effect of prostaglandin of the A series: inhibition of vaccinia virus replication in cultured cells. J. gen. Virol.63 (1982) 435–440.
Santoro, M. G., Jaffe, B. M., and Esteban, M., Prostaglandin A inhibits the replication of vesicular stomatitis virus: effect on virus glycoprotein. J. gen. Virol.64 (1983) 2797–2081.
Santoro, M. G., Crisari, A., Benedetto, A., and Amici, C., Modulation of the growth of a human erythroleukemic cell line (K562) by prostaglandins: antiproliferative action of prostaglandin A. Cancer Res.46 (1986) 6073–6077.
Santoro, M. G., Favalli, C., Mastino, A., Jaffe, B. M., Esteban, M., and Garaci, E., Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus. Archs Virol.99 (1988) 89–100.
Santoro, M. G., Garaci, E., and Amici, C., Prostaglandins with antiproliferative activity induce the synthesis of a heat shock protein in human cells. Proc. natl Acad. Sci. USA86 (1989) 8407–8411.
Santoro, M. G., Amici, C., Elia, G., Benedetto, A., and Garaci, E., Inhibition of virus protein glycosylation as the mechanism of the antiviral action of prostaglandin A1 in Sendai virus-infected cells. J. gen. Virol.70 (1989) 789–800.
Santoro, M. G., Garaci, E., and Amici, C., Induction of hsp70 by prostaglandins, in: Stress Proteins: Induction and Function, pp. 27–44. Eds M. J. Schlesinger, E. Garaci and M. G. Santoro. Springer-Verlag, Berlin 1990.
Santoro, M. G., Garaci, E., and Amici, C., Induction of heat shock protein synthesis by prostaglandins with antineoplastic and antiviral activity, in Advances in Prostaglandin, Thromboxane, and Leukotriene Research, vol. 21. pp. 867–874. Eds B. Samuelsson, P. Y. Wong and F. F. Sun. Raven Press, New York 1991.
Santoro, M. G., Amici, C., De Marco, A., Pica, F., and Rossi, A., Control of virus replication by cyclopentenone prostaglandins: a multistage process, associated with induction of heat shock protein synthesis. Antiviral Res.20 S(I) (1993) 158.
Sarnow, P., Translation of glucose-regulated protein 78/immunoglobulin heavy-chain binding protein mRNA is increased in poliovirus-infected cells at a time when cap-dependent translation of cellular mRNAs is inhibited. Proc. natl Acad. Sci. USA86 (1989) 5795–5799.
Sawtell, N. M., and Thompson, R. L., Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. J. Virol.66 (1992) 2150–2156.
Schlesinger, M. J., Ryan, C., Sadis, S., and Hightower, L. E., In vitro inhibition of nascent polypeptide formation by HSP70 proteins, in: Heat Shock Proteins, pp. 111–117. Eds B. Maresca, S. Lindquist Springer-Verlag, Berlin 1991.
Stanley, S. K., Bressler, P. B., Poli, G., and Fauci, A. S., Heat shock induction of HIV production from chronically infected promonocytic and T cell lines. J. Immun.145 (1990) 1120–1126.
Tyrrell, D., Barrow, I., and Arthus, J., Local hyperthermia benefits natural and experimental common colds. Br. med. J.298 (1989) 1280–1283.
Vane, J. R., Antiinflammatory drugs and the arachidonic acid cascade, in: Prostaglandins in Cancer Research, pp. 12–28. Eds E. Garaci, R. Paoletti and M. G. Santoro. Springer, Berlin-Heidelberg 1987.
Vidal, S., and Kolakofsky, D., Modified model for the switch from Sendai virus transcription to replication. J. Virol.63 (1989) 1951–1958.
Watowich, S. S., Morimoto, R. I., and Lamb, R. A., Flux of the paramyxovirus hemagglutinin-neuraminidase glycoprotein through the endoplasmic reticulum activates transcription of the GRP78-BiP gene. J. Virol.65 (1991) 3590–3597.
White, E., Spector, D., and Welch, W., Differential distribution of the adenovirus E1A proteins and colocalization of E1A with the 70-kilodalton cellular heat shock protein in infected cells. J. Virol.62 (1988) 4153–4166.
Williams, G. T., McClanahan, T. K., and Morimoto, R. I., Ela transactivation of the human hsp70 promoter is mediated through the basal trascriptional complex. Molec. cell. Biol.9 (1989) 2574–2587.
Wu, B. J., Hurst, H. C., Jones, N. C., and Morimoto, R. I., The E1A 13S product of adenovirus-5 activates transcription of the cellular human hsp70 gene. Molec. cell. Biol.6 (1986) 2994–2999.
Yamamoto, N., Rahman, M., Fukushima, M., Maeno, K., and Nishiyama, Y., Involvement of prostaglandin-induced proteins in the inhibition of herpes simplex virus replication. Biochem. biophys. Res. Commun.158 (1989) 189–194.
Yura, Y., Terashima, K., Iga, H., Kondo, Y., Yanagawa, T., Yoshida, H., Hiyashi, Y., and Sato, M., Macromolecular synthesis at the early stage of herpes simplex type 2 (HSV 2) latency in a human neuroblastoma cell line IMR-32: repression of late viral polypeptide synthesis and accumulation of cellular heat-shock proteins. Archs Virol.96 (1987) 17–28.
Zerbini, M., Musiani, M., and La Placa, M., Effect of heat shock on Epstein-Barr virus and cytomegalovirus expression. J. gen. Virol.66 (1985) 633–636.
Zylicz, M., LeBwitz, J. H., McMacken, R., and Georgopoulos, C., The dnaK protein of Escherichia coli processes an ATPase and autophosphorylating activity and is essential in an in vitro DNA replication system. Proc. natl Acad. Sci. USA80 (1983) 6431–6435.
Zylicz, M., and Georgopoulos, C., Purification and properties of the Escherichia coli dnaK replication protein. J. biol. Chem.259 (1984) 8820–8825.
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Santoro, M.G. Heat shock proteins and virus replication: hsp70s as mediators of the antiviral effects of prostaglandins. Experientia 50, 1039–1047 (1994). https://doi.org/10.1007/BF01923459
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DOI: https://doi.org/10.1007/BF01923459