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. 2008 Jun;82(11):5501-9.
doi: 10.1128/JVI.02555-07. Epub 2008 Apr 2.

Paucity of CD4+ CCR5+ T cells may prevent transmission of simian immunodeficiency virus in natural nonhuman primate hosts by breast-feeding

Ivona Pandrea  1 , Richard Onanga, Sandrine Souquiere, Augustin Mouinga-Ondéme, Olivier Bourry, Maria Makuwa, Pierre Rouquet, Guido Silvestri, François Simon, Pierre Roques, Cristian Apetrei
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Paucity of CD4+ CCR5+ T cells may prevent transmission of simian immunodeficiency virus in natural nonhuman primate hosts by breast-feeding

Ivona Pandrea et al. J Virol. 2008 Jun.

Abstract

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 x 10(6) to 8 x 10(8) RNA copies/ml) and paralleled the high VLs in milk (4.7 x 10(4) to 5.6 x 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.

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Figures

FIG. 1.
FIG. 1.
Viral RNA copy numbers in plasma of SIVmnd-1-infected mandrill dames. The detection limit of the assay was 5 × 102 copies/ml.
FIG. 2.
FIG. 2.
Kinetics of major lymphocyte populations and subsets (absolute counts) in peripheral blood from SIVmnd-1-infected mandrill dames. SIVmnd-1 infection induced significant depletion at the peak of viral replication of CD4+ T cells (a). During chronic infection, the quantity of CD4+ T cells rebounded to near preinfection values (a). At the peak of viral replication, the effector memory CD4+ T cells (defined as CD4+ CD28−) were significantly depleted in peripheral blood (b). No significant changes were observed for the kinetics of CD8+ T cells (c) and CD20 cells (d).
FIG. 3.
FIG. 3.
Kinetic expression immune activation, expressed as the percentage of HLA-DR MAbs upon CD4+ (a) and CD8+ T lymphocytes (b) and of cell proliferation, expressed as the percentage of Ki-67 upon CD4+ (c) and CD8+ T lymphocytes (d) in peripheral blood of SIVmnd-1-infected mandrill dames.
FIG. 4.
FIG. 4.
SIVmnd-1 pol nested PCR results for offspring of experimentally infected mandrill dames at the end of the lactation period (day 180 p.i.). None of the nested PCRs from offspring samples was positive (lanes 1 to 6). Positive (PC) and negative (NC) controls of the PCR are also shown.
FIG. 5.
FIG. 5.
CCR5 expression on CD4+ T cells of uninfected baby (n = 12; aged >6 months) versus adult (n = 23) mandrills (a) and representative flow cytometry plots of CCR5 expression on CD4+ T cells in a young AGM versus that in an adult AGM (b). Significantly lower CCR5 expression was observed with young versus adult animals. Note that CCR5 expression is already low in African NHPs compared to that in rhesus macaques or in humans (45).
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