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

Int Conf AIDS 1998 Jun 28-Jul 3; 12:25 (abstract no. 11215)

Markham RB, Khanna KV, Whaley K, Zeitlin L, Ford D
Johns Hopkins University, Baltimore, MD 21205, USA.

OBJECTIVE: To develop an animal model of vaginal transmission of HIV-1 which can be used to study mechanisms of transmission and intervention strategies.

METHODS: Using a SCID-Hu-PBL mouse model of HIV-1 infection, we studied hormonal status, the necessity for cell-associated virus, and viral phenotype as variables in the vaginal transmission of HIV-1 SCID mice reconstituted intraperitoneally at Day 0 with 5 x 107 human PBMC were administered progestin (5 mg, subcutaneously) and seven days later were inoculated vaginally with varying doses of cell-free HIV-1 or different numbers of cultured PBMC that had been infected with either SI or NSI strains of HIV-1. Cells or virus were inoculated into anaesthetized mice in a volume of 30 microliters using a pipette tip, with care being taken not to traumatize vaginal tissue. Two weeks post-inoculation, mice were euthanized and peritoneal cells were collected by lavage. Polymerase chain reaction and culture (p24 antigen detection) were performed to assay for the presence of HIV-1.

RESULTS: Neither progestin-treated nor untreated mice could be infected by intravaginal inoculation of up to 10(6) TCID50 of cell free HIVBa-L. Infection was established with HIVBa-L-infected PBMC in progestin-treated mice in a dose-dependent manner. Transmission using NSI (HIVBa-L) virus infected cells was significantly more efficient than that using SI (HIVMN) virus infected cells, but at high cell inocula infection could be established with SI variants. TABULAR DATA, SEE ABSTRACT VOLUME

CONCLUSION: HIV-1-infected cells, but not cell-free virus, can transmit infection by the vaginal route in progestin-treated Hu-PBL-SCID mice. The pattern of viral phenotype selection in transmission parallels that observed in the clinical setting. This animal system which models sexual transmission of HIV-1 should prove useful for the development of strategies for the interruption of sexual transmission of HIV-1 and for elucidating transmission mechanisms.

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