Mandrillus sphinx, a large primate living in Cameroon and Gabon and belonging to the Papionini tribe, was reported to be infected by a simian immunodeficiency virus (SIV) (SIVmndGB1) as early as 1988. Here, we have identified a second, highly divergent SIVmnd (designated SIVmnd-2). Genomic organization differs between the two viral types; SIVmnd-2 has the additional vpx gene, like other SIVs naturally infecting the Papionini tribe (SIVsm and SIVrcm) and in contrast to the other SIVmnd type (here designated SIVmnd-1), which is more closely related to SIVs infecting l'hoest (Cercopithecus lhoesti lhoesti) and sun-tailed (Cercopithecus lhoesti solatus) monkeys. Importantly, our epidemiological studies indicate a high prevalence of both types of SIVmnd; all 10 sexually mature wild-living monkeys and 3 out of 17 wild-born juveniles tested were infected. The geographic distribution of SIVmnd seems to be distinct for the two types: SIVmnd-1 viruses were exclusively identified in mandrills from central and southern Gabon, whereas SIVmnd-2 viruses were identified in monkeys from northern and western Gabon, as well as in Cameroon. SIVmnd-2 full-length sequence analysis, together with analysis of partial sequences from SIVmnd-1 and SIVmnd-2 from wild-born or wild-living mandrills, shows that the gag and pol regions of SIVmnd-2 are closest to those of SIVrcm, isolated from red-capped mangabeys (Cercocebus torquatus), while the env gene is closest to that of SIVmnd-1. pol and env sequence analyses of SIV from a related Papionini species, the drill (Mandrillus leucophaeus), shows a closer relationship of SIVdrl to SIVmnd-2 than to SIVmnd-1. Epidemiological surveys of human immunodeficiency virus revealed a case in Cameroon of a human infected by a virus serologically related to SIVmnd, raising the possibility that mandrills represent a viral reservoir for humans similar to sooty mangabeys in Western Africa and chimpanzees in Central Africa.
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...
Due to an error in manuscript preparation, an incorrect shRNA sequence for IRS2 was published. The correct hairpin sequence is a 19-nt stretch beginning from nt 703 of the published IRS2 cDNA sequence (XM_357863). The oligonucleotides cloned into the U6 construct for the IRS2U6 adenovirus are as follows: tcgagGTGACGCTGCAGCTTATGAttcaagagaTCATAAGCTGCAGCGTCACttttt (forward) and ctagAAAAAGTGACGCTGCAGCTTATGAtctcttgaaTCATAAGCTGCAGCGTCACc (reverse). In addition, the shRNA cassettes were cloned into the adenoviral cosmid pAxcwit, which lacks a promoter, and not the cosmid pAxCAwtit, as published..The authors regret this error.
Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 ؋ 10 6 to 2 ؋ 10 8 RNA equivalents/ml). Viremia then decreased 10-to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 ؋ 10 5 RNA equivalents/ml). The CD4 ؉ cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8؉ cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8؉ cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4؉ and CD8؉ cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.
Viral loads were investigated in SIVmnd-1 chronically infected mandrills and the results were compared with those previously observed in other nonpathogenic natural SIV infections. Four naturally and 11 experimentally SIVmnd-1-infected mandrills from a semi-free-ranging colony were studied during the chronic phase of infection. Four SIVmnd-1-infected wild mandrills were also included for comparison. Twelve uninfected mandrills were used as controls. Viral loads in all chronically infected mandrills ranged from 10(5) to 9 x 10(5) copies/ml and antibody titers ranged from 200 to 14,400 and 200 to 12,800 for anti-V3 and anti-gp36, respectively. There were no differences between groups of wild and captive mandrills. Both parameters were stable during the follow-up, and no clinical signs of immune suppression were observed. Chronic SIVmnd-1-infected mandrills presented slight increases in CD20+ and CD28+/CD8+ cell counts, and a slight decrease in CD4+/CD3+ cell counts. A slight CD4+/CD3+ cell depletion was also observed in old uninfected controls. Similar to other nonpathogenic models of lentiviral infection, these results show a persistent high level of SIVmnd-1 replication during chronic infection of mandrills, with minimal effects on T cell subpopulations.
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