1887

Abstract

Infection of macaques with attenuated simian immunodeficiency virus (SIV) induces potent superinfection resistance that may be applicable to the development of an AIDS vaccine but little information exists concerning the conditions necessary for the induction of this vaccine effect. We report that only a high dose of attenuated SIVmac protected macaques against intravenous challenge with more virulent virus 15 weeks after primary infection. Three of four animals given 2000–20000 TCID of SIVmacC8, a molecular clone of SIVmac251(32H) with a 12 bp deletion in the gene, essentially resisted superinfection with uncloned SIVmac. In two animals challenge virus was never detected by PCR and in one animal challenge virus was detected on one occasion only. Although animals given 2– 200 TCID of attenuated virus were superinfected they were spared from the loss of CD4 cells seen in infected naive controls. Protection from superinfection did not correlate with immune responses, including the levels of virus-specific antibodies or virus-neutralizing activity measured on the day of challenge; although, after superinfection challenge, Nef-specific CTL responses were detected only in animals infected with high doses of attenuated SIV. Unexpectedly, cell-associated virus loads 2 weeks after inoculation were significantly lower in animals infected with a high dose of attenuated SIV compared to those in animals infected with a low dose. Our results suggest that the early dynamics of infection with attenuated virus influence superinfection resistance.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-8-1935
1998-08-01
2022-10-04
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/8/9714241.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-8-1935&mimeType=html&fmt=ahah

References

  1. Ahmed-Ansari A., Powell J. D., Jenson P. E., Yehuda-Cohen T., McClure H. M., Andersen D., Fultz P. N., Sell K. W. 1990; Requirements for simian immunodeficiency virus antigen-specific in vitro proliferation of T cells from infected rhesus and sooty mangabeys. AIDS 4:399–407
    [Google Scholar]
  2. Almond N., Kent K., Cranage M., Rud E., Clarke B., Stott E. J. 1995; Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells. Lancet 345:1342–1344
    [Google Scholar]
  3. Baba T. W., Jeong Y. S., Penninck D., Bronson R., Greene M. F., Ruprecht R. M. 1995; Pathogenicity of live attenuated SIV after mucosal infection of neonatal macaques. Science 267:1820–1825
    [Google Scholar]
  4. Benveniste O., Vaslin B., LeGrand R., Cheret A., Matheux F., Theodoro F., Cranage M. P., Dormont D. 1996; Comparative interleukin (IL)-2/interferon (IFN)-γ and IL-4/IL-10 responses during acute infection of macaques inoculated with attenuated nef-truncated or pathogenic SIVmac251 virus. Proceedings of the National Academy of Sciences, USA 93:3658–3663
    [Google Scholar]
  5. Clements J. E., Montelaro R. C., Zink M. C., Amedee A. M., Miller S., Trichel A. M., Jagerski B., Hauer D., Martin L. N., Bohm R. P., Murphey-Corb M. 1995; Cross-protective immune responses induced in rhesus macaques by immunization with attenuated macrophage-tropic simian immunodeficiency virus. Journal of Virology 69:2737–2744
    [Google Scholar]
  6. Clerici M., Clark E. A., Polacino P., Axberg I., Kuller L. R., Casey N. I., Morton W. R., Shearer G. M., Benveniste R. E. 1994; T-cell proliferation to subinfectious SIV correlates with lack of infection after challenge of macaques. AIDS 8:1391–1395
    [Google Scholar]
  7. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P. 1995; Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811–1815
    [Google Scholar]
  8. Cranage M. P., Whatmore A. M., Sharpe S. A., Cook N., Polyanskaya N., Leech S., Smith J. D., Rud E. W., Dennis M. J., Hall G. A. 1997; Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa. Virology 229:143–154
    [Google Scholar]
  9. Daniel M. D., Kirchhoff F., Czajak S. C., Sehgal P. K., Desrosiers R. C. 1992; Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258:1938–1941
    [Google Scholar]
  10. Dittmer U., Luke W., Stahl-Hennig C., Coulibaly C., Petry H., Bodemer H., Hunsmann G., Voss G. 1994; Early helper T-cell dysfunction in simian immunodeficiency virus but not in human immunodeficiency virus type-2-infected macaques. Journal of Medical Primatology 23:298–303
    [Google Scholar]
  11. Feng N., Burns J. W., Bracy L., Greenberg H. B. 1994; Comparison of mucosal and systemic humoral immune responses and subsequent protection in mice orally inoculated with a homologous or a heterologous rotavirus. Journal of Virology 68:7766–7773
    [Google Scholar]
  12. Flamand A., Coulon P., Pepin M., Blancou J., Rollin P., Portnoi D. 1984; Immunogenic and protective power of avirulent mutants of rabies virus selected with neutralizing monoclonal antibodies. In Modern Approaches to Vaccines pp. 289–294 Chanock R. M., Lerner R. A. Edited by Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  13. Gallimore A., Cranage M., Cook N., Almond N., Bootman J., Rud E., Silvera P., Dennis M., Corcoran T., Stott J., McMichael A., Gotch F. 1995; Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques. Nature Medicine 1:1167–1173
    [Google Scholar]
  14. Kitchin P. A., Almond N., Szotyori Z., Fromholc C. E., McAlpine L., Silvera P., Stott E. J., Cranage M., Baskerville A., Schild G. 1990; The use of the polymerase chain reaction for the detection of simian immunodeficiency virus in experimentally infected macaques. Journal of Virological Methods 28:85–100
    [Google Scholar]
  15. McGraw T. P., Vowels B. R., Gardner M. B., Ahmed-Ansari A., Gershwin M. E. 1990; Simian immunodeficiency virus-specific T cell- mediated proliferative response of infected macaques. AIDS 4:191–198
    [Google Scholar]
  16. Mackowicz C. 1992; CD8+ cell anti-HIV activity: nonlytic suppression of virus replication. AIDS Research and Human Retroviruses 8:1039–1050
    [Google Scholar]
  17. McNeal M. M., Sheridan J. F., Ward R. L. 1992; Active protection against rotavirus infection of mice following intraperitoneal immunization. Virology 191:150–157
    [Google Scholar]
  18. Marthas M. L., Sujipto S., Higgins J., Lohman B., Torten J., Luciw P. A., Marx P., Pederson N. C. 1990; Immunization with a live attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV. Journal of Virology 64:3694–3700
    [Google Scholar]
  19. Mercadal C. M., Slaoui M., Brown S. M., Rouse B. T. 1993; Efficacy of the herpes simplex virus types 1 and 2 mutant viruses to confer protection against zosteriform spread in mice. Viral Immunology 6:35–42
    [Google Scholar]
  20. Miller C. J., Marthas M., Torten J., Alexander N. J., Moore J. P., Doncel G. F., Hendrickx A. G. 1994; Intravaginal inoculation of rhesus macaques with cell-free simian immunodeficiency virus results in persistent or transient viremia. Journal of Virology 68:6391–6400
    [Google Scholar]
  21. Miller C. J., McChesney M. B., Lu X., Dailey P. J., Chutkowski C., Lu D., Brosio P., Roberts B., Lu Y. 1997; Rhesus macaques previously infected with simian/human immunodeficiency virus are protected from vaginal challenge with pathogenic SIVmac239. Journal of Virology 71:1911–1921
    [Google Scholar]
  22. Mitchell T., Risser R. 1992; Interference established in mice by infection with Friend murine leukemia virus. Journal of Virology 66:5696–5702
    [Google Scholar]
  23. Norley S., Beer B., Binninger-Schinzel D., Cosma C., Kurth R. 1996; Protection from pathogenic SIVmac challenge following short-term infection with a nef-deficient attenuated virus. Virology 219:195–205
    [Google Scholar]
  24. Pauza C. D., Emau P., Salvato M. S., Trivedi P., MacKenzie D., Malkovsky M., Uno H., Schultz K. T. 1993; Pathogenesis of SIVmac251 after atraumatic inoculation of the rectal mucosa in rhesus monkeys. Journal of Medical Primatology 22:154–161
    [Google Scholar]
  25. Paxton W. A., Martin S. R., Tse D., O’Brien T. R., Skurnick J., VanDevanter N. L., Padian N., Braun J. F., Kotler D. P., Wolinsky S. M., Koup R. A. 1996; Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures. Nature Medicine 2:412–417
    [Google Scholar]
  26. Polyanskaya P., Sharpe S., Cook N., Leech S., Banks J., Dennis M., Hall G., Stott J., Cranage M. 1997; Anti-major histocompatibility complex antibody responses to simian B cells do not protect macaques against SIVmac infection. AIDS Research and Human Retroviruses 13:923–931
    [Google Scholar]
  27. Putkonen P., Thorstensson R., Albert J., Hild K., Norrby E., Biberfeld P., Biberfeld G. 1990; Infection of cynomolgus monkeys with HIV-2 protects against pathogenic consequences of a subsequent simian immunodeficiency virus infection. AIDS 4:783–789
    [Google Scholar]
  28. Putkonen P., Nilsson C., Mäkitalo B., Biberfeld G., Thorstensson R., Cranage M., Rud E. 1996; Immunization with live attenuated SIVmac can protect macaques against mucosal infection with SIVsm. In Vaccines 96 pp. 235–241 Brown F., Norrby E., Burton D., Mekalanos J. Edited by Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  29. Rose J., Silvera P., Flanagan B., Kitchin P., Almond N. 1995; The development of PCR based assays for the detection and differentiation of simian immunodeficiency virus in vivo . Journal of Virological Methods 51:229–239
    [Google Scholar]
  30. Rud E. W., Cranage M., Yon J., Quirk J., Ogilvie L., Cook N., Webster S., Dennis M., Clarke B. E. 1994; Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variants. Journal of General Virology 75:529–543
    [Google Scholar]
  31. Sharpe S. 1997 T cell responses to simian immunodeficiency virus PhD thesis Open University, UK:
    [Google Scholar]
  32. Stahl-Hennig C., Dittmer U., Nißlein T., Petry H., Jurkiewicz E., Fuchs D., Wachter H., Mätz-Rensing K., Kuhn E.-M., Kaup F.-J., Rud E. W., Hunsmann G. 1996; Rapid development of vaccine protection in macaques by live-attenuated simian immunodeficiency virus. Journal of General Virology 77:2969–2981
    [Google Scholar]
  33. Trivedi P., Horejsh D., Hinds S. B., Hinds P. W. II Wu M. S., Salvato M. S., Pauza C. D. 1996; Intrarectal transmission of simian immunodeficiency virus in rhesus macaques : selective amplification and host responses to transient and persistent viraemia. Journal of Virology 70:6876–6883
    [Google Scholar]
  34. Whatmore A. M., Cook N., Hall G. A., Sharpe S., Rud E. W., Cranage M. P. 1995; Repair and evolution of nef in vivo modulates simian immunodeficiency virus virulence. Journal of Virology 69:5117–5123
    [Google Scholar]
  35. Wyand M. S., Manson K. H., Garcia-Moll M., Montefiori D., Desrosiers R. C. 1996; Vaccine protection by a triple deletion mutant of simian immunodeficiency virus. Journal of Virology 70:3724–3733
    [Google Scholar]
  36. Wyand M. S., Manson K. H., Lackner A. A., Desrosiers R. C. 1997; Resistance of neonatal monkeys to live attenuated vaccine strains of simian immunodeficiency virus. Nature Medicine 3:32–36
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-8-1935
Loading
/content/journal/jgv/10.1099/0022-1317-79-8-1935
Loading

Data & Media loading...

Most cited this month 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