INFECTION OF MONKEYS BY INTRAVAGINAL INOCULATION OF SIV

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In order to demonstrate that our cryopreserved SIV isolate is useful for mucosal inoculations via the intravaginal route, two doses of SIV/Delta B670 grown in human PBMC were inoculated intravaginally into adult females the undiluted stock (5 monkeys) and a 1:10 dilution (6 monkeys). The menstrual cycle of 10 of the 11 monkeys was regulated prior by hormone injections so that each female was in the same stage of the cycle at the time of virus inoculation in order to both control for this variable, and also to assure a near-neutral vaginal pH at the time of inoculation. During the early follicular phase of the estrus cycle the action of estrogen results in an increase in glycogen in vaginal secretions which lactobacilli convert to acid, leading to a decrease in pH which may be destructive to virus. Also during this period the vaginal epithelium is thicker. After ovulation, the level of progesterone increases markedly resulting in higher pH of secretions, and the vaginal epithelium becomes thinner. The menstrual cycle was regulated by progesterone injections. Sixteen days after menses began, the monkeys were treated with progesterone for 13 days, and virus was inoculated intravaginally on the 12th day of treatment, ensuring that the vagina was under full progesterone influence at the time of inoculation. SIV was atraumatically introduced into the vagina using a pediatric nasogastric tube. The hormonal regulation procedure was followed for all of the monkeys except one, in which menses were not observed during this period. Four of the 5 monkeys receiving the undiluted inoculum and 5 of the 6 monkeys receiving the 1:10 dilution of virus clearly became infected, as determined by the development of serum viral antigenemia and/or by repeated positive PCR reactions in DNA extracted from PBMCs, lymph node, and tissue biopsy specimens (cervix, vagina, rectum). One of the monkeys which became infected was the one whose menstrual cycle had not been regulated, and which was in menses at the time of inoculation. These results indicate that some monkeys are more refractory to infection by the intravaginal route than others. This individual variability in susceptibility to infection could be related to the individual variability that we have observed in disease progression.