PAUCITY OF CD4+CCR5+ T CELLS AND BREASTFEEDING SIV TRANSMISSION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Simian immunodeficiency virus (SIV) persistence in wild populations of African nonhuman primates (NHPs) may occur through horizontal and vertical transmission. However, the mechanism(s) and timing of the latter type of transmission have not been investigated to date. Here we present the first study of SIV transmissibility by breast-feeding in an African NHP host. Methods: Six mandrill dames were infected with plasma containing 300 50% tissue culture infective doses of SIVmnd-1 on the day after delivery. All female mandrills became infected, as demonstrated by both plasma viral loads (VLs) and anti-SIVmnd-1 seroconversion. Results and Dicussion: Neither fever nor lymphadenopathy was observed. At the peak of SIVmnd-1 viral replication (days 7 to 10 postinoculation), plasma VLs were high (8 ¿ 10^6 to 8 ¿ 10^8 RNA copies/ml) and paralleled the high VLs in milk (4.7 ¿ 10^4 to 5.6 ¿ 105 RNA/ml). However, at the end of the breast-feeding period, after 6 months of follow-up, no sign of infection was observed for the offspring. Later on, during a 4-year follow-up examination, two of the offspring showed virological evidence of SIVmnd-1 infection. Both animals seroconverted at least 6 months after the interruption of lactation. In conclusion, despite extensive viral replication in mandrill mothers and high levels of free virus in milk, no SIVmnd-1 transmission was detectable at the time of breast-feeding or during the following months. Since we observed a markedly lower expression of CCR5 on the CD4+ T cells of young mandrills and African green monkeys than on those of adults, we propose that low levels of this viral coreceptor on CD4+ T cells may be involved in the lack of breast-feeding transmission in natural hosts of SIVs.