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. 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. 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 ؋ 10 5 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.
Pathogenic human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections of humans and macaques are characterized by the invariable progression to AIDS in a variable time frame (25). The hallmarks of this infection are as follows: (i) continuous depletion of CD4ϩ T cells in peripheral blood (6,23) and at the mucosal sites (7, 34); (ii) continuous viral replication (26,51,68), in which set point viral load (VL) levels are predictive of the progression to AIDS (24, 32, 35-37); and (iii) high levels of immune activation (20, 64), the magnitude of which is also predictive of disease progression (20, 64).In contrast, natural SIV infection of numerous African nonhuman primate (NHP) hosts, including mandrills, African green monkeys (AGMs), and sooty mangabeys (SMs), usually does not progress to AIDS and is characterized by (i) high prevalences in the wild for most species (1,4,29,50,52,57); (ii) an active viral replication, with set point levels similar to or even higher than those reported for pathogenic infection (40,41,44,(47)(48)(49)(59)(60)(61); (iii) a transient depletion of CD4 ϩ T cells in peripheral blood during the primary infection, with a rebound to near preinfection levels during the chronic stage (41,44,47,59); (iv) a significant CD4 ϩ T-cell depletion in the intestine that can be partially restor...