Archives of Virology

, Volume 99, Issue 1–2, pp 89–100 | Cite as

Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus

  • M. G. Santoro
  • C. Favalli
  • A. Mastino
  • B. M. Jaffe
  • M. Esteban
  • E. Garaci
Original Papers


We have previously shown that prostaglandins of the A series potently inhibit virus replication in several virus-host systems in vitro. In the present report we have studied the effect of a long-acting synthetic analog of PGA, 16,16-dimethyl-PGA2 (Di-M-PGA2), on virus infection in vivo, using as a model Balb/c mice infected with influenza A (PR8) virus. Depending upon the dose of viral inoculum, PR8 virus caused the death of 50 to 100% of the animals in a period of 8–20 days. Di-M-PGA2-treatment significantly increased mouse survival by an average of 40%, independently of the dose of inoculum and the age of the animals. The fact that Di-M-PGA2-treatment decreased virus titers in the lungs and did not alter the host immune response, suggested that PGA's therapeutic action was due to suppression of virus replication. Finally, two anti-inflammatory compounds, which inhibit prostaglandin synthesis, aspirin and indomethacin, were shown not to significantly alter mouse survival in this system.


Influenza Aspirin Prostaglandin Indomethacin Virus Replication 
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  1. 1.
    Ankel H, Mittnacht S, Jacobsen H (1985) Antiviral activity of Prostaglandin A on encephalomyocarditis virus-infected cells: a unique effect unrelated to interferon. J Gen Virol 66: 2355–2364Google Scholar
  2. 2.
    Bonta LI, de Vos CJ (1965) The effect of estradiol-16,17-dihemisuccinate on vascular permeability as evaluated in the rat paw edema test. Acta Endocrinol 49: 403–407Google Scholar
  3. 3.
    Dixon NJ, Massey FJ (1957) Introduction to statistical analysis. Mc Graw-Hill, New York, p 280–289Google Scholar
  4. 4.
    Dore-Duffy P (1982) Differential effect of prostaglandins and other products of arachidonic acid metabolism on measles virus replication in Vero cells. Prost Leuko Med 8: 73–82Google Scholar
  5. 5.
    Favalli C, Garaci E, Santoro MG, Santucci L, Jaffe BM (1980) The effect of PGA1 on the immune response in B-16 melanoma-bearing mice. Prostaglandins 19: 587–593Google Scholar
  6. 6.
    Favalli C, Garaci E, Etheredge E, Santoro MG, Jaffe BM (1980) Influence of PGE on the immune response in melanoma-bearing mice. J Immunol 125: 897–902Google Scholar
  7. 7.
    Goodwin JS, Webb DR (1980) Regulation of the immunoresponse by prostaglandins. Clin Immunol Immunopathol 15: 106–121Google Scholar
  8. 8.
    Harbour DA, Blyth WA, Hill TJ (1978) Prostaglandins enhance spread of herpes simplex virus in cell culture. J Gen Virol 41: 87–95Google Scholar
  9. 9.
    Herberman RB, Nunn ME, Laurin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity. Int J Cancer 16: 216–224Google Scholar
  10. 10.
    Inglot A (1969) Comparisons of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs. J Gen Virol 4: 203–204Google Scholar
  11. 11.
    Kurane I, Tsuchiya Y, Sekizawa T, Kumagai K (1984) Inhibition by indomethacin of in vitro reactivation of latent herpes simplex virus type 1 in murine trigeminal ganglia. J Gen Virol 65: 1665–1674Google Scholar
  12. 12.
    Lennette EH, Schmidt NJ (1979) Diagnostic procedures for viral, rickettsial and chlamydial infections, 5th edn. A.P.H.A., Washington, D.C., pp 603–605Google Scholar
  13. 13.
    Luczak M, Gumulka W, Szmigielski S, Korbecki M (1975) Inhibition of multiplication of parainfluenza 3 virus in prostaglandin-treated WISH cells. Arch Virol 49: 377–380Google Scholar
  14. 14.
    Pottathil R, Chandrabose KA, Cuatrecasas P, Lang DJ (1980) Establishment of the interferon-mediated antiviral state: role of fatty acid cycloxygenase. Proc Natl Acad Sci USA 77: 5437–5446Google Scholar
  15. 15.
    Rodriguez-Boulan E (1983) Polarized assembly of enveloped viruses from cultured epithelial cells. Methods Enzymol 98: 486–501Google Scholar
  16. 16.
    Santoro MG, Benedetto A, Carruba G, Garaci E, Jaffe BM (1980) Prostaglandin A compounds as antiviral agents. Science 209: 1032–1034Google Scholar
  17. 17.
    Santoro MG, Carruba G, Garaci E, Jaffe BM, Benedetto A (1981) Prostaglandins of the A series inhibit Sendai virus replication in cultured cells. J Gen Virol 53: 75–83Google Scholar
  18. 18.
    Santoro MG, Jaffe BM, Garaci E, Esteban M (1982) Antiviral effect of prostaglandins of the A series: inhibition of vaccinia virus replication in cultured cells. J Gen Virol 63: 435–440Google Scholar
  19. 19.
    Santoro MG, Jaffe BM, Esteban M (1983) Prostaglandin A1 inhibits the replication of Vesicular Stomatitis Virus: effect on virus glycoprotein. J Gen Virol 64: 2797–2801Google Scholar
  20. 20.
    Santoro MG, Jaffe BM, Paez E, Esteban M (1983) The relationship between the antiviral action of interferon and prostaglandins in virus-infected murine cells. Biochem Biophys Res Comm 116: 442–448Google Scholar
  21. 21.
    Santoro MG (1987) Involvement of protein synthesis in the antiproliferative and the antiviral action of prostaglandins. In: Garaci E, Paoletti R, Santoro MG (eds) Prostaglandins in cancer research. Springer, Berlin Heidelberg New York Tokyo, pp 97–114Google Scholar
  22. 22.
    Smith HW, Cook JK, Parsell ZE (1985) The experimental infection of chickens with mixtures of infectious Bronchitis Virus and Escherichia Coli. J Gen Virol 66: 777–786Google Scholar
  23. 23.
    Stanley ED, Jackson GG, Panusarh C, Rubenis M, Diroda U (1975) Increased virus shedding with aspirin treatment of rhinovirus infection. J Am Med Ass 231: 1248–1251Google Scholar
  24. 24.
    Trofatter K, Daniels C (1980) Effect of prostaglandins and cyclic adenosine 3′,5′-monophosphate modulators on herpes simplex virus growth and interferon response in human cells. Infect Immun 27: 158–164Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • M. G. Santoro
    • 1
  • C. Favalli
    • 2
  • A. Mastino
    • 2
  • B. M. Jaffe
    • 3
  • M. Esteban
    • 4
  • E. Garaci
    • 2
  1. 1.Institute of Experimental Medicine, C.N.R.II University of RomeRomeItaly
  2. 2.Department of Experimental MedicineII University of RomeRomeItaly
  3. 3.Department of SurgeryS.U.N.Y., Downstate Medical CenterBrooklyn, New YorkU.S.A.
  4. 4.Department of BiochemistryS.U.N.Y., Downstate Medical CenterBrooklyn, New YorkU.S.A.

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