Journal ArticleDOI
Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques
Timothy W. Baba,Timothy W. Baba,Vladimir Liska,Anis H. Khimani,Nancy B. Ray,Peter J. Dailey,Dominique G. Penninck,Rod Bronson,Michael F. Greene,Harold M. McClure,Louis N. Martin,Ruth M. Ruprecht +11 more
TLDR
It is concluded that this multiply deleted SIV is pathogenic and that human AIDS vaccines built on similar prototypes may cause AIDS.Abstract:
A substantial risk in using live attenuated, multiply deleted viruses as vaccines against AIDS is their potential to induce AIDS. A mutant of the simian immunodeficiency virus (SIV) with large deletions in nef and vpr and in the negative regulatory element induced AIDS in six of eight infant macaques vaccinated orally or intravenously. Early signs of immune dysfunction were seen in the remaining two offspring. Prolonged follow-up of sixteen vaccinated adult macaques also showed resurgence of chronic viremia in four animals: two of these developed early signs of disease and one died of AIDS. We conclude that this multiply deleted SIV is pathogenic and that human AIDS vaccines built on similar prototypes may cause AIDS.read more
Citations
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Why primate models matter
Kimberley A. Phillips,Karen L. Bales,Karen L. Bales,John P. Capitanio,John P. Capitanio,Alan J Conley,Paul W. Czoty,Bert A. 't Hart,William D. Hopkins,William D. Hopkins,Shiu Lok Hu,Lisa A. Miller,Lisa A. Miller,Michael A. Nader,Peter W. Nathanielsz,Jeffrey Rogers,Jeffrey Rogers,Carol A. Shively,Mary Lou Voytko +18 more
TL;DR: Key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research are reviewed.
Journal ArticleDOI
Challenges in the development of an HIV-1 vaccine.
TL;DR: Key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine are reviewed.
Journal ArticleDOI
Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort.
Jenny Learmont,Andrew F. Geczy,John Mills,Ashton Lj,Camille Raynes-Greenow,Garsia Rj,Wayne B. Dyer,McIntyre L,Oelrichs Rb,David Ian Rhodes,Nicholas J. Deacon,John S. Sullivan +11 more
TL;DR: After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV- 1 RNA and the CD4 lymphocyte counts appear to be stable in the three subjects in whom plasmaAIDS-1 RNA remains undetectable.
Journal ArticleDOI
Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression.
Jonah B. Sacha,Chungwon Chung,Eva G. Rakasz,Sean P. Spencer,Anna K. Jonas,Alexander T. Bean,Wonhee Lee,Benjamin J. Burwitz,Jason J. Stephany,John T. Loffredo,David B. Allison,Sama Adnan,Akihiko Hoji,Nancy A. Wilson,Thomas C. Friedrich,Jeffrey D. Lifson,Otto O. Yang,David I. Watkins +17 more
TL;DR: It is shown that Gag-specific CD8+ T cells recognize infected CD4+ T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation.
Journal ArticleDOI
Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein.
TL;DR: The hypothesis that cell-surface CD4 can interact with the envelope protein present on budding HIV-1 virions to inhibit their release is supported and is likely to facilitate the spread of virus in vivo.
References
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Book
Current protocols in immunology
TL;DR: Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, and animal models of autoimmune and inflammatory diseases.
Journal ArticleDOI
1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults
Kenneth G. Castro,John W. Ward,Laurence Slutsker,James W. Buehler,Harold W. Jaffe,Ruth L. Berkelman,James Curran +6 more
TL;DR: The classification system for HIV infection is revised to emphasize the clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV-related clinical conditions and the AIDS surveillance case definition is expanded.
Journal ArticleDOI
HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease
Giuseppe Pantaleo,Cecilia Graziosi,James F. Demarest,Luca Butini,Maria Montroni,Cecil H. Fox,Jan M. Orenstein,Donald P. Kotler,Anthony S. Fauci +8 more
TL;DR: It is reported that in early-stage disease there is a dichotomy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs.
Journal ArticleDOI
Importance of the nef gene for maintenance of high virus loads and for development of AIDS.
Harry W. Kestier,Douglas J. Ringler,Kazuyasu Mori,Dennis Panicali,Prabhat K. Sehgal,Muthiah D. Daniel,Ronald C. Desrosiers +6 more
TL;DR: The results indicate that nef is required for maintaining high virus loads during the course of persistent infection in vivo and for full pathologic potential, and should become a target for antiviral drug development.
Journal ArticleDOI
Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS
Janet Embretson,Mary Zupancic,Jorge L. Ribas,Alien Burke,Paul Racz,Klara Tenner-Racz,Ashley T. Haase +6 more
TL;DR: An extraordinarily large number of latently infected CD4+ lymphocytes and macrophages are discovered throughout the lymphoid system from early to late stages of infection, and the extracellular association of HIV with follicular dendritic cells is confirmed.
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