12th International AIDS Conference Geneva, Switzerland - June 28-July 3, 1998

Int Conf AIDS 1998 Jun 28-Jul 3; 12:25-6 (abstract no. 11218)

Agy MB, Thompson J, Grant RF, Coon EM, Finn EE, Kennedy BJ, Morton WR;;; Univ. of WA Regional Primate Research Center, Seattle 98195, USA.

BACKGROUND: To develop an acutely pathogenic SHIV isolate to be used as a macaque challenge virus in vaccine and drug efficacy studies and to gain insight into the host restrictions of the primate lentiviruses. The SHIV used in these studies was originally described by Li et al. (1992) and contains env, tat, rev and vpu from HIV-1 in a SIVmac-239 backbone.

METHODS: We determined the macaque infectious dose of SHIV HXBc2 in M. nemestrina and used that virus to challenge HIV-1-env vaccinated macaques. During several of these early experiments, 22 naïve M. nemestrina were inoculated with SHIV HXBc2. Of these, most were consistently virus culture positive through 1 year and 3 showed a gradual but steady declines in CD4+ T cells. Blood from 2 of the CD4-declining animals was transfused into 2 naïve macaques. A virus stock was prepared from bone marrow cells isolated from one of these animals and was inoculated into two naïve macaques. Overlapping 3O-5O halves and nearly full length provirus were cloned from amplified DNA obtained from the stock-production culture and transfected into T-293 cells.

RESULTS: In contrast to the gradual CD4 cell decline of the original macaques, the 2 blood recipient animals experienced rapid CD4 decline during the first 6 weeks. RNA PCR analysis revealed virus titers at 5 weeks 100 times that of the donor animals at the time of transfusion. Macaques inoculated with the bone marrow-derived stock also experienced rapid CD4 declines and high plasma virus levels. The transfected cell culture supernatants contained significant levels of SIV p27 antigen.

CONCLUSION: SHIV HXBc2 was pathogenic in M. nemestrina, causing spontaneous CD4 T-cell decline in approximately 10% of the infected animals. An acutely pathogenic SHIV stock has been developed following a single blood passage. Molecular clones have been recovered from this stock.

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