title: Specific passage of simian immunodeficiency virus from end-stage disease results in accelerated progression to AIDS in rhesus macaques.
abstract: To determine whether passage of late-stage variants of simian immunodeficiency virus (SIV) would lead to a more virulent infection and rapid disease progression, a study was designed to examine the effects of selective transmission of SIV from late-stage cases of AIDS in Macaca mulatta. In a uniform group of 10 age-matched animals from the same genetic breeding stock infected with SIV(B670), it took 7 months before one of the ten animals developed AIDS. Passage of virus taken from this animal immediately prior to death resulted in death of the recipient due to AIDS within 4 months. Again, subsequent passage of virus taken late in disease resulted in an accelerated disease course, with AIDS developing within 2.5 and 1.8 months in two recipients. The fourth passage of virus taken late in disease from the most rapid progressor (1.8 months) resulted in AIDS developing in this recipient within 1 month of infection. During each consecutive passage in vivo, the loss of memory T cells became more acute. Evidence that the virus became more virulent with selective passage of late-stage variants was provided by the markedly increased levels of both plasma antigen and viral RNA. Subsequent in vivo passage from end-stage AIDS selected for a strain of SIV capable of causing the acute development of AIDS as rapidly as 1 month post-infection. The pathology of acute AIDS in these cases closely resembled that seen after a chronic disease course.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Lange Kleiweg 157, 2288 GJ, Rijswijk, The Netherlands1.
authors.forename: Lennart
authors.initials: L
authors.lastname: Holterman
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Lange Kleiweg 157, 2288 GJ, Rijswijk, The Netherlands1.
authors.forename: Henk
authors.initials: H
authors.lastname: Niphuis
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Lange Kleiweg 157, 2288 GJ, Rijswijk, The Netherlands1.
authors.forename: Peter J F
authors.initials: PJF
authors.lastname: Ten Haaft
authors.affiliation: Department of Human Retrovirology, Academic Medical Centre, Amsterdam, The Netherlands2.
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.affiliation: Department of Pathology, Tulane Regional Primate Research Centre, Tulane University, Covington, LA 70433, USA3.
authors.forename: Gary
authors.initials: G
authors.lastname: Baskin
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Lange Kleiweg 157, 2288 GJ, Rijswijk, The Netherlands1.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D005434:Flow Cytometry; D007156:Immunologic Memory; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity* / Q000502:physiology; D019562:Viral Load; D014774:Virulence
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral