1887

Journal of General Virology header logo

Volume 91, Issue 3

Beta interferon plus gamma interferon efficiently reduces acyclovir-resistant herpes simplex virus infection in mice in a T-cell-independent manner Free

Abstract

Acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) causes severe diseases in immunocompromised patients, so identification of new therapies is needed. Interferons (IFNs) are used to treat several other viral infections in the clinic, and IFN- and IFN- are known to cooperatively reduce wild-type HSV-1 replication in the corneas of immunocompetent mice. Because IFN- has been shown to exert an antiviral effect mostly through T cells, whether combined IFN treatment can still inhibit ACV-resistant HSV-1 replication, especially in immunocompromised hosts, is unknown. The present study evaluated the efficacy of combined IFN treatment on ACV-resistant HSV-1 mutants. results showed that IFN- acted synergistically with IFN- to inhibit HSV-1 replication in both human and mouse cell lines. Some ACV-resistant mutants were actually hypersensitive to combined IFN treatment. results showed that topical treatment with a low dose of IFN- plus IFN- (200 U each) on mouse corneas efficiently reduced the viral loads by up to 4, 4 and 3 logs, respectively, in the eyes, trigeminal ganglia and brainstems of wild-type and also immunocompromised nude mice infected or co-infected with ACV-resistant HSV-1 in a manner independent of T cells. A highly efficient reduction in HSV acute replication by combined IFN treatment led to a dramatic decrease in subsequent virus reactivation from neural tissues, trigeminal ganglia, brainstems and spinal cords of latently infected mice. Thus, a combination of IFN- and IFN- could be a potential treatment for ACV-resistant HSV-1 in immunocompromised patients.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.016964-0
2010-03-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/3/591.html?itemId=/content/journal/jgv/10.1099/vir.0.016964-0&mimeType=html&fmt=ahah

References

  1. Adler H., Beland J. L., Del-Pan N. C., Kobzik L., Sobel R. A., Rimm I. J. 1999; In the absence of T cells, natural killer cells protect from mortality due to HSV-1 encephalitis. J Neuroimmunol 93:208–213 [CrossRef]
     [Google Scholar]
  2. Al-Khatib K., Williams B. R., Silverman R. H., Halford W., Carr D. J. 2004; Distinctive roles for 2′,5′-oligoadenylate synthetases and double-stranded RNA-dependent protein kinase R in the in vivo antiviral effect of an adenoviral vector expressing murine IFN- β . J Immunol 172:5638–5647 [CrossRef]
     [Google Scholar]
  3. Biron C. A., Nguyen K. B., Pien G. C., Cousens L. P., Salazar-Mather T. P. 1999; Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220 [CrossRef]
     [Google Scholar]
  4. Casrouge A., Zhang S. Y., Eidenschenk C., Jouanguy E., Puel A., Yang K., Alcais A., Picard C., Mahfoufi N. et al. 2006; Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314:308–312 [CrossRef]
     [Google Scholar]
  5. Cheeseman S. H., Rubin R. H., Stewart J. A., Tolkoff-Rubin N. E., Cosimi A. B., Cantell K., Gilbert J., Winkle S., Herrin J. T. et al. 1979; Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections. N Engl J Med 300:1345–1349 [CrossRef]
     [Google Scholar]
  6. Chen S. H., Lin Y. W., Griffiths A., Huang W. Y., Chen S. H. 2006a; Competition and complementation between thymidine kinase-negative and wild-type herpes simplex virus during co-infection of mouse trigeminal ganglia. J Gen Virol 87:3495–3502 [CrossRef]
     [Google Scholar]
  7. Chen S. H., Yao H. W., Huang W. Y., Hsu K. S., Lei H. Y., Shiau A. L., Chen S. H. 2006b; Efficient reactivation of latent herpes simplex virus from mouse central nervous system tissues. J Virol 80:12387–12392 [CrossRef]
     [Google Scholar]
  8. Cheng H., Tumpey T. M., Staats H. F., van Rooijen N., Oakes J. E., Lausch R. N. 2000; Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection. Invest Ophthalmol Vis Sci 41:1402–1409
     [Google Scholar]
  9. Chou J., Chen J. J., Gross M., Roizman B. 1995; Association of a M r 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2 α and premature shutoff of protein synthesis after infection with γ 134.5− mutants of herpes simplex virus 1. Proc Natl Acad Sci U S A 92:10516–10520 [CrossRef]
     [Google Scholar]
  10. Christophers J., Clayton J., Craske J., Ward R., Collins P., Trowbridge M., Darby G. 1998; Survey of resistance of herpes simplex virus to acyclovir in northwest England. Antimicrob Agents Chemother 42:868–872
     [Google Scholar]
  11. Coen D. M., Schaffer P. A. 2003; Antiherpesvirus drugs: a promising spectrum of new drugs and drug targets. Nat Rev Drug Discov 2:278–288 [CrossRef]
     [Google Scholar]
  12. Coen D. M., Kosz-Vnenchak M., Jacobson J. G., Leib D. A., Bogard C. L., Schaffer P. A., Tyler K. L., Knipe D. M. 1989; Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci U S A 86:4736–4740 [CrossRef]
     [Google Scholar]
  13. Corey L., Whitley R. J., Stone E. F., Mohan K. 1988; Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome. Lancet 1:1–4
     [Google Scholar]
  14. Davar G., Kramer M. F., Garber D., Roca A. L., Andersen J. K., Bebrin W., Coen D. M., Kosz-Vnenchak M., Knipe D. M. et al. 1994; Comparative efficacy of expression of genes delivered to mouse sensory neurons with herpes virus vectors. J Comp Neurol 339:3–11 [CrossRef]
     [Google Scholar]
  15. Dienstag J. L. 2008; Hepatitis B virus infection. N Engl J Med 359:1486–1500 [CrossRef]
     [Google Scholar]
  16. Fleming H. E., Coen D. M. 1984; Herpes simplex virus mutants resistant to arabinosyladenine in the presence of deoxycoformycin. Antimicrob Agents Chemother 26:382–387 [CrossRef]
     [Google Scholar]
  17. Griffiths A., Chen S. H., Horsburgh B. C., Coen D. M. 2003; Translational compensation of a frameshift mutation affecting herpes simplex virus thymidine kinase is sufficient to permit reactivation from latency. J Virol 77:4703–4709 [CrossRef]
     [Google Scholar]
  18. Hoofnagle J. H., di Bisceglie A. M. 1997; The treatment of chronic viral hepatitis. N Engl J Med 336:347–356 [CrossRef]
     [Google Scholar]
  19. Horsburgh B. C., Chen S. H., Hu A., Mulamba G. B., Burns W. H., Coen D. M. 1998; Recurrent acyclovir-resistant herpes simplex in an immunocompromised patient: can strain differences compensate for loss of thymidine kinase in pathogenesis?. J Infect Dis 178:618–625 [CrossRef]
     [Google Scholar]
  20. Kassim S. H., Rajasagi N. K., Zhao X., Chervenak R., Jennings S. R. 2006; In vivo ablation of CD11c-positive dendritic cells increases susceptibility to herpes simplex virus type 1 infection and diminishes NK and T-cell responses. J Virol 80:3985–3993 [CrossRef]
     [Google Scholar]
  21. Larkin J., Jin L., Farmen M., Venable D., Huang Y., Tan S. L., Glass J. I. 2003; Synergistic antiviral activity of human interferon combinations in the hepatitis C virus replicon system. J Interferon Cytokine Res 23:247–257 [CrossRef]
     [Google Scholar]
  22. Le Bon A., Tough D. F. 2002; Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol 14:432–436 [CrossRef]
     [Google Scholar]
  23. Mossman K. L., Saffran H. A., Smiley J. R. 2000; Herpes simplex virus ICP0 mutants are hypersensitive to interferon. J Virol 74:2052–2056 [CrossRef]
     [Google Scholar]
  24. Pazin G. J., Armstrong J. A., Lam M. T., Tarr G. C., Jannetta P. J., Ho M. 1979; Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root. N Engl J Med 301:225–230 [CrossRef]
     [Google Scholar]
  25. Pelosi E., Rozenberg F., Coen D. M., Tyler K. L. 1998; A herpes simplex virus DNA polymerase mutation that specifically attenuates neurovirulence in mice. Virology 252:364–372 [CrossRef]
     [Google Scholar]
  26. Peng T., Zhu J., Hwangbo Y., Corey L., Bumgarner R. E. 2008; Independent and cooperative antiviral actions of beta interferon and gamma interferon against herpes simplex virus replication in primary human fibroblasts. J Virol 82:1934–1945 [CrossRef]
     [Google Scholar]
  27. Roizman B., Knipe D. M., Whitley R. J. 2007; Herpes simplex viruses. In Fields Virology , 5th edn. pp 2501–2601 Edited by Knipe D. M., Howley P. Philadelphia: Lippincott Williams & Wilkins;
     [Google Scholar]
  28. Sainz B. Jr, Halford W. P. 2002; Alpha/beta interferon and gamma interferon synergize to inhibit the replication of herpes simplex virus type 1. J Virol 76:11541–11550 [CrossRef]
     [Google Scholar]
  29. Sainz B. Jr, Mossel E. C., Peters C. J., Garry R. F. 2004; Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-CoV).. Virology 329:11–17 [CrossRef]
     [Google Scholar]
  30. Sainz B. Jr, LaMarca H. L., Garry R. F., Morris C. A. 2005; Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma. Virol J 2:14–26 [CrossRef]
     [Google Scholar]
  31. Schoenborn J. R., Wilson C. B. 2007; Regulation of interferon- γ during innate and adaptive immune responses. Adv Immunol 96:41–101
     [Google Scholar]
  32. Staats H. F., Oakes J. E., Lausch R. N. 1991; Anti-glycoprotein D monoclonal antibody protects against herpes simplex virus type 1-induced diseases in mice functionally depleted of selected T-cell subsets or asialo GM1+ cells. J Virol 65:6008–6014
     [Google Scholar]
  33. Stanberry L. R., Jorgensen D. M., Nahmias A. J. 1997; Herpes simplex viruses 1 and 2. In Viral Infections of Humans: Epidemiology and Control . pp 419–454 Edited by Evans A. S., Kaslow R. A. New York: Springer;
  34. Stranska R., van Loon A. M., Polman M., Beersma M. F., Bredius R. G., Lankester A. C., Meijer E., Schuurman R. 2004; Genotypic and phenotypic characterization of acyclovir-resistant herpes simplex viruses isolated from haematopoietic stem cell transplant recipients. Antivir Ther 9:565–575
     [Google Scholar]
  35. Tenser R. B., Edris W. A. 1987; Trigeminal ganglion infection by thymidine kinase-negative mutants of herpes simplex virus after in vivo complementation. J Virol 61:2171–2174
     [Google Scholar]
  36. Virelizier J. L., Arenzana-Seisdedos F. 1985; Immunological functions of macrophages and their regulation by interferons. Med Biol 63:149–159
     [Google Scholar]
  37. Wang K., Mahalingam G., Hoover S. E., Mont E. K., Holland S. M., Cohen J. I., Straus S. E. 2007; Diverse herpes simplex virus type 1 thymidine kinase mutants in individual human neurons and ganglia. J Virol 81:6817–6826 [CrossRef]
     [Google Scholar]
  38. Whitley R. J. 2002; Herpes simplex virus infection. Semin Pediatr Infect Dis 13:6–11 [CrossRef]
     [Google Scholar]
  39. Zhang S. Y., Jouanguy E., Ugolini S., Smahi A., Elain G., Romero P., Segal D., Sancho-Shimizu V., Lorenzo L. et al. 2007; TLR3 deficiency in patients with herpes simplex encephalitis. Science 317:1522–1527 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.016964-0
Loading
Beta interferon plus gamma interferon efficiently reduces acyclovir-resistant herpes simplex virus infection in mice in a T-cell-independent manner
J. Gen. Virol. 91, 591 (2010); https://doi.org/10.1099/vir.0.016964-0
/content/journal/jgv/10.1099/vir.0.016964-0
/content/journal/jgv/10.1099/vir.0.016964-0
Loading

Data & Media loading...

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