1887

Abstract

Of the viral factors that are proposed to influence the rate of progression to AIDS, the role of infectious dose remains unresolved. Intravenous infection of outbred with various doses of simian immunodeficiency virus isolate 8980 (SIV) revealed an endpoint from which an infectious dose 50 (ID) was defined. In the six infected animals, the time to develop AIDS was variable with a spectrum of rapid, intermediate and slow progressors. High and sustained plasma viraemia with marked loss of CD4 T-cells was a distinguishing feature between rapid versus intermediate and slow progressors. Animals that received the highest doses did not develop the highest sustained viral loads, nor did they progress more rapidly to disease. Similarly, animals infected with lower doses did not uniformly develop lower viral loads or progress more slowly to AIDS. Furthermore, compiled data from more than 21 animals infected with different doses of the same virus administered by the same route failed to reveal any correlation of infectious dose with survival. Indeed, host factors of these outbred animals, rather than dose of the initial inoculum, were probably an important factor influencing the rate of disease progression in each individual animal. Comparison of animals infected with SIV, from which SIV was derived, revealed marked differences in disease progression. Clearly, although dose did not influence viral loads nor disease progression, the virulence of the initial inoculum was a major determinant of the rate of progression to AIDS.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-7-1719
2000-07-01
2019-12-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/7/0811719a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-7-1719&mimeType=html&fmt=ahah

References

  1. Asjo, B., Morfeldt-Manson, L., Albert, J., Biberfeld, G., Karlsson, A., Lidman, K. & Fenyo, E. M. (1986). Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet ii, 660–662.
  2. Baba, T. W., Jeong, Y. S., Pennick, 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.[CrossRef]
    [Google Scholar]
  3. Baskin, G. B., Bontrop, R. E., Niphuis, H., Noort, R., Rice, J. & Heeney, J. L. ( 1997; ). Correlation of major histocompatibility complex with opportunistic infections in simian immunodeficiency virus-infected rhesus monkeys. Laboratory Investigation 77, 305-309.
    [Google Scholar]
  4. Baskin, G. B., Murphey-Corb, M., Watson, E. A. & Martin, L. N. ( 1988; ). Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/delta. Veterinary Pathology 25, 456-467.[CrossRef]
    [Google Scholar]
  5. Bogers, W. M., Dubbes, R., Ten Haaft, P., Niphuis, H., Cheng-Mayer, C., Stahl-Hennig, C., Hunsmann, G., Kuwata, T., Hayami, M., Jones, S., Ranjbar, S., Almond, N., Stott, J., Rosenwirth, B. & Heeney, J. L. ( 1997; ). Comparison of in vitro and in vivo infectivity of different clade B HIV-1 envelope chimeric simian/human immunodeficiency viruses in Macaca mulatta. Virology 236, 110-117.[CrossRef]
    [Google Scholar]
  6. Bogers, W. M., Koornstra, W. H., Dubbes, R. H., Ten Haaft, P. J., Verstrepen, B. E., Jhagjhoorsingh, S. S., Haaksma, A. G., Niphuis, H., Laman, J. D., Norley, S., Schuitemaker, H., Goudsmit, J., Hunsmann, G., Heeney, J. L. & Wigzell, H. ( 1998; ). Characteristics of primary infection of a European human immunodeficiency virus type 1 clade B isolate in chimpanzees. Journal of General Virology 79, 2895-2903.
    [Google Scholar]
  7. Bontrop, R. E., Otting, N., Niphuis, H., Noort, R., Teeuwsen, V. & Heeney, J. L. ( 1996; ). The role of major histocompatibility complex polymorphisms on SIV infection in rhesus macaques. Immunology Letters 51, 35-38.[CrossRef]
    [Google Scholar]
  8. Buchbinder, S. P., Katz, M. H., Hessol, N. A., O’Malley, P. M. & Holmberg, S. D. ( 1994; ). Long-term HIV-1 infection without immunologic progression. AIDS 8, 1123-1128.[CrossRef]
    [Google Scholar]
  9. Cameron, P. U., Mallal, S. A., French, M. A. & Dawkins, R. L. ( 1990; ). Major histocompatibility complex genes influence the outcome of HIV infection. Ancestral haplotypes with C4 null alleles explain diverse HLA associations. Human Immunology 29, 282-295.[CrossRef]
    [Google Scholar]
  10. Cao, Y., Qin, L., Zhang, L., Safrit, J. & Ho, D. D. ( 1995; ). Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. New England Journal of Medicine 332, 201-208.[CrossRef]
    [Google Scholar]
  11. Chaisson, R. E., Keruly, J. C. & Moore, R. D. ( 1995; ). Race, sex, drug use, and progression of human immunodeficiency virus disease. New England Journal of Medicine 333, 751-756.[CrossRef]
    [Google Scholar]
  12. Coffin, J. M. ( 1986; ). Genetic variation in AIDS viruses. Cell 46, 1-4.
    [Google Scholar]
  13. Deacon, N. J., Tsykin, A., Solomon, A., Smith, K., Ludford-Menting, M., Hooker, D. J., McPhee, D. A., Greenway, A. L., Ellett, A., Chatfield, C. and others ( 1995; ). Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 270, 988–991.[CrossRef]
    [Google Scholar]
  14. Dykhuizen, M., Mitchen, J. L., Montefiori, D. C., Thomson, J., Acker, L., Lardy, H. & Pauza, C. D. ( 1998; ). Determinants of disease in the simian immunodeficiency virus-infected rhesus macaque: characterizing animals with low antibody responses and rapid progression. Journal of General Virology 79, 2461-2467.
    [Google Scholar]
  15. Edmonson, P., Murphey-Corb, M., Martin, L. N., Delahunty, C., Heeney, J., Kornfeld, H., Donahue, P. R., Learn, G. H., Hood, L. & Mullins, J. I. ( 1998; ). Evolution of a simian immunodeficiency virus pathogen. Journal of Virology 72, 405-414.
    [Google Scholar]
  16. Fauci, A. S. ( 1996; ). Host factors in the pathogenesis of HIV disease. Antibiotics and Chemotherapy 48, 4-12.
    [Google Scholar]
  17. Fowler, S. L., Harrison, C. J., Myers, M. G. & Stanberry, L. R. ( 1992; ). Outcome of herpes simplex virus type 2 infection in guinea pigs. Journal of Medical Virology 36, 303-308.[CrossRef]
    [Google Scholar]
  18. Fultz, P. N. ( 1993; ). Nonhuman primate models for AIDS. Clinical Infectious Diseases 17, 230-235.[CrossRef]
    [Google Scholar]
  19. Geretti, A. M., Hulskotte, E. & Osterhaus, A. D. ( 1998; ). Cytotoxic T lymphocytes in AIDS pathogenesis: lessons to be learned from the macaque model of simian immunodeficiency virus infection. Journal of General Virology 79, 415-421.
    [Google Scholar]
  20. Ginsberg, H. S., Moldawer, L. L., Sehgal, P. B., Redington, M., Kilian, P. L., Chanock, R. M. & Prince, G. A. ( 1991; ). A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. Proceedings of the National Academy of Sciences, USA 88, 1651-1655.[CrossRef]
    [Google Scholar]
  21. Heeney, J. L. ( 1996; ). Primate models for AIDS vaccine development. AIDS 10, 115-122.[CrossRef]
    [Google Scholar]
  22. Holterman, L., Niphuis, H., Ten Haaft, P. J. F., Goudsmit, J., Baskin, G. & Heeney, J. L. ( 1999; ). Specific passage of simian immunodeficiency virus from end-stage disease results in accelerated progression to AIDS in rhesus macaques. Journal of General Virology 80, 3089-3097.
    [Google Scholar]
  23. Jilbert, A. R., Botten, J. A., Miller, D. S., Bertram, E. M., Hall, P. M., Kotlarski, J. & Burrell, C. J. ( 1998; ). Characterization of age- and dose-related outcomes of duck hepatitis B virus infection. Virology 244, 273-282.[CrossRef]
    [Google Scholar]
  24. Jordan, M. C. ( 1978; ). Interstitial pneumonia and subclinical infection after intranasal inoculation of murine cytomegalovirus. Infection and Immunity 21, 275-280.
    [Google Scholar]
  25. Kaslow, R. A., Carrington, M., Apple, R., Park, L., Munoz, A., Saah, A. J., Goedert, J. J., Winkler, C., O’Brien, S. J., Rinaldo, C., Detels, R., Blattner, W., Phair, J., Erlich, H. & Mann, D. L. ( 1996; ). Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nature Medicine 2, 405-411.[CrossRef]
    [Google Scholar]
  26. Kaur, A., Grant, R. M., Means, R. E., McClure, H., Feinberg, M. & Johnson, R. P. ( 1998; ). Diverse host responses and outcomes following simian immunodeficiency virus SIVmac239 infection in sooty mangabeys and rhesus macaques. Journal of Virology 72, 9597-9611.
    [Google Scholar]
  27. Keet, I. P., Krol, A., Klein, M. R., Veugelers, P., de Wit, J., Roos, M., Koot, M., Goudsmit, J., Miedema, F. & Coutinho, R. A. ( 1994; ). Characteristics of long-term asymptomatic infection with human immunodeficiency virus type 1 in men with normal and low CD4+ cell counts. Journal of Infectious Diseases 169, 1236-1243.[CrossRef]
    [Google Scholar]
  28. Kestler, H. W. D., Ringler, D. J., Mori, K., Panicali, D. L., Sehgal, P. K., Daniel, M. D. & Desrosiers, R. C. ( 1991; ). Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65, 651-662.[CrossRef]
    [Google Scholar]
  29. Kimata, J. T., Kuller, L., Anderson, D. B., Dailey, P. & Overbaugh, J. ( 1999; ). Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression. Nature Medicine 5, 535-541.[CrossRef]
    [Google Scholar]
  30. Kirchhoff, F., Carl, S., Sopper, S., Sauermann, U., Matz-Rensing, K. & Stahl-Hennig, C. ( 1999; ). Selection of the R17Y substitution in SIVmac239 nef coincided with a dramatic increase in plasma viremia and rapid progression to death. Virology 254, 61-70.[CrossRef]
    [Google Scholar]
  31. Laurence, J. ( 1990; ). Molecular interactions among herpesviruses and human immunodeficiency viruses. Journal of Infectious Diseases 162, 338-346.[CrossRef]
    [Google Scholar]
  32. Letvin, N. L., Daniel, M. D., Sehgal, P. K., Desrosiers, R. C., Hunt, R. D., Waldron, L. M., MacKey, J. J., Schmidt, D. K., Chalifoux, L. V. & King, N. W. ( 1985; ). Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science 230, 71-73.[CrossRef]
    [Google Scholar]
  33. Levy, J. A. ( 1993; ). HIV pathogenesis and long-term survival. AIDS 7, 1401-1410.[CrossRef]
    [Google Scholar]
  34. Lifson, A. R., Buchbinder, S. P., Sheppard, H. W., Mawle, A. C., Wilber, J. C., Stanley, M., Hart, C. E., Hessol, N. A. & Holmberg, S. D. ( 1991; ). Long-term human immunodeficiency virus infection in asymptomatic homosexual and bisexual men with normal CD4+ lymphocyte counts: immunologic and virologic characteristics. Journal of Infectious Diseases 163, 959-965.[CrossRef]
    [Google Scholar]
  35. McCarthy, G. M. ( 1992; ). Host factors associated with HIV-related oral candidiasis. A review. Oral Surgery Oral Medicine Oral Pathology 73, 181-186.[CrossRef]
    [Google Scholar]
  36. Marthas, M. L., Ramos, R. A., Lohman, B. L., Van-Rompay, K. K., Unger, R. E., Miller, C. J., Banapour, B., Pedersen, N. C. & Luciw, P. A. ( 1993; ). Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac. Journal of Virology 67, 6047-6055.
    [Google Scholar]
  37. Marthas, M. L., Van Rompay, K. K., Otsyula, M., Miller, C. J., Canfield, D. R., Pedersen, N. C. & McChesney, M. B. ( 1995; ). Viral factors determine progression to AIDS in simian immunodeficiency virus-infected newborn rhesus macaques. Journal of Virology 69, 4198-4205.
    [Google Scholar]
  38. Mellors, J. W., Rinaldo, C.Jr, Gupta, P., White, R. M., Todd, J. A. & Kingsley, L. A. ( 1996; ). Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272, 1167-1170.[CrossRef]
    [Google Scholar]
  39. Miller, C. J., Marthas, M., Greenier, J., Lu, D., Dailey, P. J. & Lu, Y. ( 1998; ). In vivo replication capacity rather than in vitro macrophage tropism predicts efficiency of vaginal transmission of simian immunodeficiency virus or simian/human immunodeficiency virus in rhesus macaques. Journal of Virology 72, 3248-3258.
    [Google Scholar]
  40. Montefiori, D. C., Pantaleo, G., Fink, L. M., Zhou, J. T., Zhou, J. Y., Bilska, M., Miralles, G. D. & Fauci, A. S. ( 1996; ). Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors. Journal of Infectious Diseases 173, 60-67.[CrossRef]
    [Google Scholar]
  41. Munoz, A., Kirby, A. J., He, Y. D., Margolick, J. B., Visscher, B. R., Rinaldo, C. R., Kaslow, R. A. & Phair, J. P. ( 1995; ). Long-term survivors with HIV-1 infection: incubation period and longitudinal patterns of CD4+ lymphocytes. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 8, 496-505.[CrossRef]
    [Google Scholar]
  42. Nielsen, C., Pedersen, C., Lundgren, J. D. & Gerstoft, J. ( 1993; ). Biological properties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection. AIDS 7, 1035-1040.[CrossRef]
    [Google Scholar]
  43. Niezgoda, M., Briggs, D. J., Shaddock, J., Dreesen, D. W. & Rupprecht, C. E. ( 1997; ). Pathogenesis of experimentally induced rabies in domestic ferrets. American Journal of Veterinary Research 58, 1327-1331.
    [Google Scholar]
  44. O’Brien, T. R., Blattner, W. A., Waters, D., Eyster, E., Hilgartner, M. W., Cohen, A. R., Luban, N., Hatzakis, A., Aledort, L. M., Rosenberg, P. S., Miley, W. J., Kroner, B. L. & Goedert, J. J. ( 1996; ). Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. Journal of the American Medical Association 276, 105-110.[CrossRef]
    [Google Scholar]
  45. Phair, J., Jacobson, L., Detels, R., Rinaldo, C., Saah, A., Schrager, L. & Munoz, A. ( 1992; ). Acquired immune deficiency syndrome occurring within 5 years of infection with human immunodeficiency virus type-1: the Multicenter AIDS Cohort Study. Journal of Acquired Immune Deficiency Syndromes 5, 490-496.
    [Google Scholar]
  46. Rausch, D. M., Murray, E. A. & Eiden, L. E. ( 1999; ). The SIV-infected rhesus monkey model for HIV-associated dementia and implications for neurological diseases. Journal of Leukocyte Biology 65, 466-474.
    [Google Scholar]
  47. Ruprecht, R. M., Baba, T. W., Liska, V., Ayehunie, S., Andersen, J., Montefiori, D. C., Trichel, A., Murphey-Corb, M., Martin, L., Rizvi, T. A., Bernacky, B. J., Buchl, S. J. & Keeling, M. ( 1998; ). Oral SIV, SHIV, and HIV type 1 infection. AIDS Research and Human Retroviruses 14, 97-103.
    [Google Scholar]
  48. Smith, S. M., Holland, B., Russo, C., Dailey, P. J., Marx, P. A. & Connor, R. I. ( 1999; ). Retrospective analysis of viral load and SIV antibody responses in rhesus macaques infected with pathogenic SIV: predictive value for disease progression. AIDS Research and Human Retroviruses 15, 1691-1701.[CrossRef]
    [Google Scholar]
  49. Ten Haaft, P., Verstrepen, B., Uberla, K., Rosenwirth, B. & Heeney, J. ( 1998; ). A pathogenic threshold of virus load defined in simian immunodeficiency virus- or simian-human immunodeficiency virus-infected macaques. Journal of Virology 72, 10281-10285.
    [Google Scholar]
  50. Tersmette, M., Lange, J. M., de Goede, R. E., de Wolf, F., Eeftink-Schattenkerk, J. K., Schellekens, P. T., Coutinho, R. A., Huisman, J. G., Goudsmit, J. & Miedema, F. (1989). Association between biological properties of human immunodeficiency virus variants and risk for AIDS and AIDS mortality. Lancet i, 983–985.
  51. Whetter, L. E., Ojukwu, I. C., Novembre, F. J. & Dewhurst, S. ( 1999; ). Pathogenesis of simian immunodeficiency virus infection. Journal of General Virology 80, 1557-1568.
    [Google Scholar]
  52. 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.[CrossRef]
    [Google Scholar]
  53. Zink, M. C., Spelman, J. P., Robinson, R. B. & Clements, J. E. ( 1998; ). SIV infection of macaques – modeling the progression to AIDS dementia. Journal of Neurovirology 4, 249-259.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-7-1719
Loading
/content/journal/jgv/10.1099/0022-1317-81-7-1719
Loading

Data & Media loading...

Most Cited This Month

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