This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alexander, L.
Right arrow Articles by Desrosiers, R. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alexander, L.
Right arrow Articles by Desrosiers, R. C.

 Previous Article  |  Next Article 

Journal of Virology, July 1999, p. 5814-5825, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Induction of AIDS in Rhesus Monkeys by a Recombinant Simian Immunodeficiency Virus Expressing nef of Human Immunodeficiency Virus Type 1

Louis Alexander, Zhenjian Du, Anita Y. M. Howe, Susan Czajak, and Ronald C. Desrosiers*

Received 11 January 1999/Accepted 26 March 1999

A nef gene is present in all primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus of macaque monkeys (SIVmac). However, the nef genes of HIV-1 and SIVmac exhibit minimal sequence identity, and not all properties are shared by the two. Nef sequences of SIVmac239 were replaced by four independent nef alleles of HIV-1 in a context that was optimal for expression. The sources of the HIV-1 nef sequences included NL 4-3, a variant NL 4-3 gene derived from a recombinant-infected rhesus monkey, a patient nef allele, and a nef consensus sequence. Of 16 rhesus monkeys infected with these SHIVnef chimeras, 9 maintained high viral loads for prolonged periods, as observed with the parental SIVmac239, and 6 have died with AIDS 52 to 110 weeks postinfection. Persistent high loads were observed at similar frequencies with the four different SIV recombinants that expressed these independent HIV-1 nef alleles. Infection with other recombinant SHIVnef constructions resulted in sequence changes in infected monkeys that either created an open nef reading frame or optimized the HIV-1 nef translational context. The HIV-1 nef gene was uniformly retained in all SHIVnef-infected monkeys. These results demonstrate that HIV-1 nef can substitute for SIVmac nef in vivo to produce a pathogenic infection. However, the model suffers from an inability to consistently obtain persisting high viral loads in 100% of the infected animals, as is observed with the parental SIVmac239.

* Corresponding author. Mailing address: New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Dr., Box 9102, Southborough, MA 01772-9102. Phone: (508) 624-8042. Fax: (508) 624-8190. E-mail: ronald_desrosiers{at}hms.harvard.edu.

Journal of Virology, July 1999, p. 5814-5825, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Marecki, J. C., Cool, C. D., Parr, J. E., Beckey, V. E., Luciw, P. A., Tarantal, A. F., Carville, A., Shannon, R. P., Cota-Gomez, A., Tuder, R. M., Voelkel, N. F., Flores, S. C. (2006). HIV-1 Nef Is Associated with Complex Pulmonary Vascular Lesions in SHIV-nef-infected Macaques. Am. J. Respir. Crit. Care Med. 174: 437-445 [Abstract] [Full Text]  
  • Khan, M., Jin, L., Miles, L., Bond, V. C., Powell, M. D. (2005). Chimeric Human Immunodeficiency Virus Type 1 Virions That Contain the Simian Immunodeficiency Virus nef Gene Are Cyclosporin A Resistant. J. Virol. 79: 3211-3216 [Abstract] [Full Text]  
  • Swigut, T., Alexander, L., Morgan, J., Lifson, J., Mansfield, K. G., Lang, S., Johnson, R. P., Skowronski, J., Desrosiers, R. (2004). Impact of Nef-Mediated Downregulation of Major Histocompatibility Complex Class I on Immune Response to Simian Immunodeficiency Virus. J. Virol. 78: 13335-13344 [Abstract] [Full Text]  
  • Schindler, M., Munch, J., Brenner, M., Stahl-Hennig, C., Skowronski, J., Kirchhoff, F. (2004). Comprehensive Analysis of Nef Functions Selected in Simian Immunodeficiency Virus-Infected Macaques. J. Virol. 78: 10588-10597 [Abstract] [Full Text]  
  • Costa, L. J., Zheng, Y.-H., Sabotic, J., Mak, J., Fackler, O. T., Peterlin, B. M. (2004). Nef Binds p6* in GagPol during Replication of Human Immunodeficiency Virus Type 1. J. Virol. 78: 5311-5323 [Abstract] [Full Text]  
  • Khan, M., Jin, L., Huang, M. B., Miles, L., Bond, V. C., Powell, M. D. (2004). Chimeric Human Immunodeficiency Virus Type 1 (HIV-1) Virions Containing HIV-2 or Simian Immunodeficiency Virus Nef Are Resistant to Cyclosporine Treatment. J. Virol. 78: 1843-1850 [Abstract] [Full Text]  
  • Kar, S., Cummings, P., Alexander, L. (2003). Human immunodeficiency virus type 1 Vif supports efficient primate lentivirus replication in rhesus monkey cells. J. Gen. Virol. 84: 3227-3231 [Abstract] [Full Text]  
  • Schindler, M., Wurfl, S., Benaroch, P., Greenough, T. C., Daniels, R., Easterbrook, P., Brenner, M., Munch, J., Kirchhoff, F. (2003). Down-Modulation of Mature Major Histocompatibility Complex Class II and Up-Regulation of Invariant Chain Cell Surface Expression Are Well-Conserved Functions of Human and Simian Immunodeficiency Virus nef Alleles. J. Virol. 77: 10548-10556 [Abstract] [Full Text]  
  • Munk, C., Brandt, S. M., Lucero, G., Landau, N. R. (2002). A dominant block to HIV-1 replication at reverse transcription in simian cells. Proc. Natl. Acad. Sci. USA 99: 13843-13848 [Abstract] [Full Text]  
  • Alexander, L., Aquino-DeJesus, M. J., Chan, M., Andiman, W. A. (2002). Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Replication by a Two-Amino-Acid Insertion in HIV-1 Vif from a Nonprogressing Mother and Child. J. Virol. 76: 10533-10539 [Abstract] [Full Text]  
  • Simard, M.-C., Chrobak, P., Kay, D. G., Hanna, Z., Jothy, S., Jolicoeur, P. (2002). Expression of Simian Immunodeficiency Virus nef in Immune Cells of Transgenic Mice Leads to a Severe AIDS-Like Disease. J. Virol. 76: 3981-3995 [Abstract] [Full Text]  
  • Munch, J., Adam, N., Finze, N., Stolte, N., Stahl-Hennig, C., Fuchs, D., Ten Haaft, P., Heeney, J. L., Kirchhoff, F. (2001). Simian Immunodeficiency Virus in Which nef and U3 Sequences Do Not Overlap Replicates Efficiently In Vitro and In Vivo in Rhesus Macaques. J. Virol. 75: 8137-8146 [Abstract] [Full Text]  
  • Carl, S., Greenough, T. C., Krumbiegel, M., Greenberg, M., Skowronski, J., Sullivan, J. L., Kirchhoff, F. (2001). Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions during Progression to AIDS. J. Virol. 75: 3657-3665 [Abstract] [Full Text]  
  • Alexander, L., Denekamp, L., Czajak, S., Desrosiers, R. C. (2001). Suboptimal Nucleotides in the Infectious, Pathogenic Simian Immunodeficiency Virus Clone SIVmac239. J. Virol. 75: 4019-4022 [Abstract] [Full Text]  
  • Arora, V. K., Molina, R. P., Foster, J. L., Blakemore, J. L., Chernoff, J., Fredericksen, B. L., Garcia, J. V. (2000). Lentivirus Nef Specifically Activates Pak2. J. Virol. 74: 11081-11087 [Abstract] [Full Text]  
  • Swigut, T., Iafrate, A. J., Muench, J., Kirchhoff, F., Skowronski, J. (2000). Simian and Human Immunodeficiency Virus Nef Proteins Use Different Surfaces To Downregulate Class I Major Histocompatibility Complex Antigen Expression. J. Virol. 74: 5691-5701 [Abstract] [Full Text]  
  • Alexander, L., Weiskopf, E., Greenough, T. C., Gaddis, N. C., Auerbach, M. R., Malim, M. H., O'Brien, S. J., Walker, B. D., Sullivan, J. L., Desrosiers, R. C. (2000). Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection. J. Virol. 74: 4361-4376 [Abstract] [Full Text]  
  • Messmer, D., Ignatius, R., Santisteban, C., Steinman, R. M., Pope, M. (2000). The Decreased Replicative Capacity of Simian Immunodeficiency Virus SIVmac239Delta nef Is Manifest in Cultures of Immature Dendritic Cells and T Cells. J. Virol. 74: 2406-2413 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»