1887

Abstract

Accumulating evidence suggests that exposed individuals may acquire multiple human immunodeficiency virus (HIV) infections more frequently than originally believed. As a result, circulating recombinant forms of HIV are emerging that are of particular concern in the AIDS epidemic and HIV vaccine development efforts. The aim of this study was to determine under what conditions secondary or superinfections of HIV or simian immunodeficiency virus (SIV) may be acquired under controlled settings in well-defined, non-human primate models. Retrospective analysis of macaques that had acquired apparent immunity upon infection with a defined attenuated SIV strain revealed that eight out of eight animals that were secondarily exposed to a new virus variant became infected with the new virus strain, but at low levels. Interestingly, similarly high frequencies of secondary infections were observed after early (4 months), as well as late (5 years), exposure following primary infection. As possible causes of susceptibility to secondary infections, perturbations in the immune system associated with exacerbated infections were then investigated prospectively. Results revealed that short-term immune-suppression therapy did not increase susceptibility to secondary infections. Taken together, data suggested that neither early- nor late-exposure immune-suppressive events following primary infection accounted for the observed high incidence of secondary infections. With HIV-1, the question of whether secondary infections with very closely related viral variants could occur in the chimpanzee model was addressed. In both animal models, secondary infections were confirmed, notably with relatively closely related SIV or HIV-1 strains, following a single exposure to the secondary virus strain. These findings reveal that secondary lentiviral infections may be acquired readily during different stages of primary infection, in contrast to co-infections, which are acquired at the moment of initial infection.

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2004-12-01
2019-11-14
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References

  1. Ahmed, R. K. S., Nilsson, C., Wang, Y., Lehner, T., Biberfeld, G. & Thorstensson, R. ( 1999; ). β-Chemokine production in macaques vaccinated with live attenuated virus correlates with protection against simian immunodeficiency virus (SIVsm) challenge. J Gen Virol 80, 1569–1574.
    [Google Scholar]
  2. Altfeld, M., Allen, T. M., Yu, X. G. & 13 other authors ( 2002; ). HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature 420, 434–439.[CrossRef]
    [Google Scholar]
  3. Barouch, D. H. & Letvin, N. L. ( 2002; ). Viral evolution and challenges in the development of HIV vaccines. Vaccine 20 (Suppl. 4), A66–A68.[CrossRef]
    [Google Scholar]
  4. Bogers, W. M., Niphuis, H., ten Haaft, P., Laman, J. D., Koornstra, W. & Heeney, J. L. ( 1995; ). Protection from HIV-1 envelope-bearing chimeric simian immunodeficiency virus (SHIV) in rhesus macaques infected with attenuated SIV: consequences of challenge. AIDS 9, F13–F18.
    [Google Scholar]
  5. Bogers, W. M. J. M., Koornstra, W. H., Dubbes, R. H. & 12 other authors ( 1998; ). Characteristics of primary infection of a European human immunodeficiency virus type 1 clade B isolate in chimpanzees. J Gen Virol 79, 2895–2903.
    [Google Scholar]
  6. Carrion, G., Hierholzer, J., Montano, S. & 11 other authors ( 2003; ). Circulating recombinant form CRF02_AG in South America. AIDS Res Hum Retrovir 19, 329–332.[CrossRef]
    [Google Scholar]
  7. Cornelissen, M., van den Burg, R., Zorgdrager, F. & Goudsmit, J. ( 2000; ). Spread of distinct human immunodeficiency virus type 1 AG recombinant lineages in Africa. J Gen Virol 81, 515–523.
    [Google Scholar]
  8. Cranage, M. P., Whatmore, A. M., Sharpe, S. A. & 7 other authors ( 1997; ). Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa. Virology 229, 143–154.[CrossRef]
    [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.[CrossRef]
    [Google Scholar]
  10. Delwart, E. L., Herring, B., Rodrigo, A. G. & Mullins, J. I. ( 1995; ). Genetic subtyping of human immunodeficiency virus using a heteroduplex mobility assay. In PCR Primer: a Laboratory Manual, pp. 257–273. Edited by C. W. Dieffenbach & G. S. Dveksler. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  11. Desrosiers, R. C. ( 1998; ). Prospects for live attenuated HIV. Nat Med 4, 982.
    [Google Scholar]
  12. Domingo, E., Menéndez-Arias, L., Quiñones-Mateu, M. E., Holguín, A., Gutiérrez-Rivas, M., Martínez, M. A., Quer, J., Novella, I. S. & Holland, J. J. ( 1997; ). Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants. Prog Drug Res 48, 99–128.
    [Google Scholar]
  13. Fang, G., Weiser, B., Kuiken, C. & 9 other authors ( 2004; ). Recombination following superinfection by HIV-1. AIDS 18, 153–159.[CrossRef]
    [Google Scholar]
  14. Fultz, P. N. ( 2004; ). HIV-1 superinfections: omens for vaccine efficacy? AIDS 18, 115–119.[CrossRef]
    [Google Scholar]
  15. Fultz, P. N., Srinivasan, A., Greene, C. R., Butler, D., Swenson, R. B. & McClure, H. M. ( 1987; ). Superinfection of a chimpanzee with a second strain of human immunodeficiency virus. J Virol 61, 4026–4029.
    [Google Scholar]
  16. Gundlach, B. R., Lewis, M. G., Sopper, S., Schnell, T., Sodroski, J., Stahl-Hennig, C. & Überla, K. ( 2000; ). Evidence for recombination of live, attenuated immunodeficiency virus vaccine with challenge virus to a more virulent strain. J Virol 74, 3537–3542.[CrossRef]
    [Google Scholar]
  17. Heeney, J. L. & Hahn, B. H. ( 2000; ). Vaccines and immunology: elucidating immunity to HIV-1 and current prospects for AIDS vaccine development. AIDS 14 (Suppl. 3), S125–S127.
    [Google Scholar]
  18. Heeney, J. L., Holterman, L., ten Haaft, P., Dubbes, R., Koornstra, W., Teeuwsen, V., Bourquin, P., Norley, S. & Niphuis, H. ( 1994; ). Vaccine protection and reduced virus load from heterologous macaque-propagated SIV challenge. AIDS Res Hum Retrovir 10, S117–S121.
    [Google Scholar]
  19. Holterman, L., Niphuis, H., ten Haaft, P. J., 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. J Gen Virol 80, 3089–3097.
    [Google Scholar]
  20. Holterman, L., Dubbes, R., Mullins, J. & 9 other authors ( 2001; ). Characteristics of a pathogenic molecular clone of an end-stage serum-derived variant of simian immunodeficiency virus (SIVF359). J Virol 75, 9328–9338.[CrossRef]
    [Google Scholar]
  21. Johnson, R. P., Glickman, R. L., Yang, J. Q., Kaur, A., Dion, J. T., Mulligan, M. J. & Desrosiers, R. C. ( 1997; ). Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus. J Virol 71, 7711–7718.
    [Google Scholar]
  22. Jost, S., Bernard, M.-C., Kaiser, L., Yerly, S., Hirschel, B., Samri, A., Autran, B., Goh, L.-E. & Perrin, L. ( 2002; ). A patient with HIV-1 superinfection. N Engl J Med 347, 731–736.[CrossRef]
    [Google Scholar]
  23. Khatissian, E., Monceaux, V., Cumont, M.-C., Kieny, M.-P., Aubertin, A.-M. & Hurtrel, B. ( 2001; ). Persistence of pathogenic challenge virus in macaques protected by simian immunodeficiency virus SIVmacΔnef. J Virol 75, 1507–1515.[CrossRef]
    [Google Scholar]
  24. Klenerman, P., Wu, Y. & Phillips, R. ( 2002; ). HIV: current opinion in escapology. Curr Opin Microbiol 5, 408–413.[CrossRef]
    [Google Scholar]
  25. Koelsch, K. K., Smith, D. M., Little, S. J., Ignacio, C. C., Macaranas, T. R., Brown, A. J., Petropoulos, C. J., Richman, D. D. & Wong, J. K. ( 2003; ). Clade B HIV-1 superinfection with wild-type virus after primary infection with drug-resistant clade B virus. AIDS 17, F11–F16.[CrossRef]
    [Google Scholar]
  26. Kornfeld, H., Riedel, N., Viglianti, G. A., Hirsch, V. & Mullins, J. I. ( 1987; ). Cloning of HTLV-4 and its relation to simian and human immunodeficiency viruses. Nature 326, 610–613.[CrossRef]
    [Google Scholar]
  27. Koulinska, I. N., Ndung'u, T., Mwakagile, D., Msamanga, G., Kagoma, C., Fawzi, W., Essex, M. & Renjifo, B. ( 2001; ). A new human immunodeficiency virus type 1 circulating recombinant form from Tanzania. AIDS Res Hum Retrovir 17, 423–431.[CrossRef]
    [Google Scholar]
  28. Laukkanen, T., Carr, J. K., Janssens, W. & 8 other authors ( 2000; ). Virtually full-length subtype F and F/D recombinant HIV-1 from Africa and South America. Virology 269, 95–104.[CrossRef]
    [Google Scholar]
  29. Levy, J. A. ( 2003; ). Is HIV superinfection worrisome? Lancet 361, 98–99.[CrossRef]
    [Google Scholar]
  30. Magiorkinis, G., Paraskevis, D., Vandamme, A. M., Magiorkinis, E., Sypsa, V. & Hatzakis, A. ( 2003; ). In vivo characteristics of human immunodeficiency virus type 1 intersubtype recombination: determination of hot spots and correlation with sequence similarity. J Gen Virol 84, 2715–2722.[CrossRef]
    [Google Scholar]
  31. Miedema, F., Petit, A. J. C., Terpstra, F. G. & 8 other authors ( 1988; ). Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs. J Clin Invest 82, 1908–1914.[CrossRef]
    [Google Scholar]
  32. Montavon, C., Bibollet-Ruche, F., Robertson, D. & 8 other authors ( 1999; ). The identification of a complex A/G/I/J recombinant HIV type 1 virus in various West African countries. AIDS Res Hum Retrovir 15, 1707–1712.[CrossRef]
    [Google Scholar]
  33. Mooij, P. & Heeney, J. L. ( 2001; ). Rational development of prophylactic HIV vaccines based on structural and regulatory proteins. Vaccine 20, 304–321.[CrossRef]
    [Google Scholar]
  34. Mooij, P., Bogers, W. M. J. M., Oostermeijer, H., Koornstra, W., Ten Haaft, P. J. F., Verstrepen, B. E., Van Der Auwera, G. & Heeney, J. L. ( 2000; ). Evidence for viral virulence as a predominant factor limiting human immunodeficiency virus vaccine efficacy. J Virol 74, 4017–4027.[CrossRef]
    [Google Scholar]
  35. Muller, T. F., Grebe, S. O., Neumann, M. C., Heymanns, J., Radsak, K., Sprenger, H. & Lange, H. ( 1997; ). Persistent long-term changes in lymphocyte subsets induced by polyclonal antibodies. Transplantation 64, 1432–1437.[CrossRef]
    [Google Scholar]
  36. Mwaengo, D. M. & Novembre, F. J. ( 1998; ). Molecular cloning and characterization of viruses isolated from chimpanzees with pathogenic human immunodeficiency virus type 1 infections. J Virol 72, 8976–8987.
    [Google Scholar]
  37. Nilsson, C., Makitalo, B., Thorstensson, R., Norley, S., Binninger-Schinzel, D., Cranage, M., Rud, E., Biberfeld, G. & Putkonen, P. ( 1998; ). Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm. AIDS 12, 2261–2270.[CrossRef]
    [Google Scholar]
  38. Peeters, M. & Sharp, P. M. ( 2000; ). Genetic diversity of HIV-1: the moving target. AIDS 14 (Suppl. 3), S129–S140.[CrossRef]
    [Google Scholar]
  39. Peeters, M., Toure-Kane, C. & Nkengasong, J. N. ( 2003; ). Genetic diversity of HIV in Africa: impact on diagnosis, treatment, vaccine development and trials. AIDS 17, 2547–2560.[CrossRef]
    [Google Scholar]
  40. Piyasirisilp, S., McCutchan, F. E., Carr, J. K. & 9 other authors ( 2000; ). A recent outbreak of human immunodeficiency virus type 1 infection in southern China was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form AE and a novel BC recombinant. J Virol 74, 11286–11295.[CrossRef]
    [Google Scholar]
  41. Ramos, A., Hu, D. J., Nguyen, L. & 10 other authors ( 2002; ). Intersubtype human immunodeficiency virus type 1 superinfection following seroconversion to primary infection in two injection drug users. J Virol 76, 7444–7452.[CrossRef]
    [Google Scholar]
  42. Ramos, A., Nguyen, L., Hu, D. J. & 7 other authors ( 2003; ). New HIV type 1 CRF01_AE/B recombinants displaying unique distribution of breakpoints from incident infections among injecting drug users in Thailand. AIDS Res Hum Retrovir 19, 667–674.[CrossRef]
    [Google Scholar]
  43. Sasaki, A. & Haraguchi, Y. ( 2000; ). Antigenic drift of viruses within a host: a finite site model with demographic stochasticity. J Mol Evol 51, 245–255.
    [Google Scholar]
  44. Sauermann, U., Schneider, J., Mous, J., Brunckhorst, U., Schedel, I., Jentsch, K. D. & Hunsmann, G. ( 1990; ). Molecular cloning and characterization of a German HIV-1 isolate. AIDS Res Hum Retrovir 6, 813–823.[CrossRef]
    [Google Scholar]
  45. Sharpe, S. A., Whatmore, A. M., Hall, G. A. & Cranage, M. P. ( 1997; ). Macaques infected with attenuated simian immunodeficiency virus resist superinfection with virulence-revertant virus. J Gen Virol 78, 1923–1927.
    [Google Scholar]
  46. Stebbings, R. J., Almond, N. M., Stott, E. J. & 9 other authors ( 2002; ). Mechanisms of protection induced by attenuated simian immunodeficiency virus. V. No evidence for lymphocyte-regulated cytokine responses upon rechallenge Virology 296, 338–353.[CrossRef]
    [Google Scholar]
  47. Takebe, Y., Motomura, K., Tatsumi, M., Lwin, H. H., Zaw, M. & Kusagawa, S. ( 2003; ). High prevalence of diverse forms of HIV-1 intersubtype recombinants in Central Myanmar: geographical hot spot of extensive recombination. AIDS 17, 2077–2087.[CrossRef]
    [Google Scholar]
  48. Teeuwsen, V. J. P., Siebelink, K. H. J., de Wolf, F., Goudsmit, J., UytdeHaag, F. G. C. M. & Osterhaus, A. D. M. E. ( 1990; ). Impairment of in vitro immune responses occurs within 3 months after HIV-1 seroconversion. AIDS 4, 77–81.[CrossRef]
    [Google Scholar]
  49. ten Haaft, P., Cornelissen, M., Goudsmit, J. & 7 other authors ( 1995; ). Virus load in chimpanzees infected with human immunodeficiency virus type 1: effect of pre-exposure vaccination. J Gen Virol 76, 1015–1020.[CrossRef]
    [Google Scholar]
  50. ten Haaft, P. J. F., Holterman, L., Niphuis, H., Dubbes, R., Koornstra, W. & Heeney, J. L. ( 1996; ). Evidence of circulating pathogenic SIV following challenge of macaques vaccinated with live attenuated SIV. In Vaccines 96, pp. 219–223. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  51. ten Haaft, P., Verstrepen, B., Überla, K., Rosenwirth, B. & Heeney, J. ( 1998; ). A pathogenic threshold of virus load defined in simian immunodeficiency virus- or simian-human immunodeficiency virus-infected macaques. J Virol 72, 10281–10285.
    [Google Scholar]
  52. Titti, F., Sernicola, L., Geraci, A. & 12 other authors ( 1997; ). Live attenuated simian immunodeficiency virus prevents super-infection by cloned SIVmac251 in cynomolgus monkeys. J Gen Virol 78, 2529–2539.
    [Google Scholar]
  53. Tscherning-Casper, C., Dolcini, G., Mauclère, P., Fenyö, E. M., Barré-Sinoussi, F., Albert, J. & Menu, E. ( 2000; ). Evidence of the existence of a new circulating recombinant form of HIV type 1 subtype A/J in Cameroon. The European Network on the Study of In Utero Transmission of HIV-1. AIDS Res Hum Retrovir 16, 1313–1318.[CrossRef]
    [Google Scholar]
  54. Watson, A., Ranchalis, J., Travis, B., McClure, J., Sutton, W., Johnson, P. R., Hu, S.-L. & Haigwood, N. L. ( 1997; ). Plasma viremia in macaques infected with simian immunodeficiency virus: plasma viral load early in infection predicts survival. J Virol 71, 284–290.
    [Google Scholar]
  55. Wooley, D. P., Smith, R. A., Czajak, S. & Desrosiers, R. C. ( 1997; ). Direct demonstration of retroviral recombination in a rhesus monkey. J Virol 71, 9650–9653.
    [Google Scholar]
  56. Wyand, M. S., Manson, K., Montefiori, D. C., Lifson, J. D., Johnson, R. P. & Desrosiers, R. C. ( 1999; ). Protection by live, attenuated simian immunodeficiency virus against heterologous challenge. J Virol 73, 8356–8363.
    [Google Scholar]
  57. Yang, R., Xia, X., Kusagawa, S., Zhang, C., Ben, K. & Takebe, Y. ( 2002; ). On-going generation of multiple forms of HIV-1 intersubtype recombinants in the Yunnan Province of China. AIDS 16, 1401–1407.[CrossRef]
    [Google Scholar]
  58. Yang, R., Kusagawa, S., Zhang, C., Xia, X., Ben, K. & Takebe, Y. ( 2003; ). Identification and characterization of a new class of human immunodeficiency virus type 1 recombinants comprised of two circulating recombinant forms, CRF07_BC and CRF08_BC, in China. J Virol 77, 685–695.[CrossRef]
    [Google Scholar]
  59. Yu, X.-F., Liu, W., Chen, J. & 7 other authors ( 2001; ). Rapid dissemination of a novel B/C recombinant HIV-1 among injection drug users in southern China. AIDS 15, 523–525.[CrossRef]
    [Google Scholar]
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