猿猴免疫缺陷病毒_(大猩猩)具有跨物种以及在人群中传播的能力

SIVgor has the capacity of zoonotic transmission and subsequent spread between humans

目的西非大猩猩(Gorilla gorilla gorilla)是猿猴免疫缺陷病毒大猩猩(SIVgor)的天然宿主。本研究旨在确定SIVgor能否传播给人类并在人体内复制。方法首先将25只6~8周的NOD/SCIDIL-2Rγc^(-/-)小鼠通过尾静脉注射移植人造血干细胞入免疫缺陷小鼠中,构建有完整人造血系统的人源化小鼠。然后通过静脉(5只)、直肠(7只)和阴道(5只)三种途径将人源化小鼠暴露于9×10~4TCIU的SIVgor,每2周检测人源化小鼠体内HIV的病毒载量和CD4^(+)T淋巴细胞水平,评估三种暴露途径SIVgor的传播能力、体内复制能力以及对CD4^(+)T淋巴细胞的杀伤力。结果静脉暴露后,SIVgor在人源化小鼠中高效复制,病毒载量达到与HIV感染的人类相当。直肠和阴道接种病毒也导致人源化小鼠感染SIVgor。尽管SIVgor在人源化小鼠体内高水平复制,但外周血中人CD4^(+)T淋巴细胞水平在三种暴露途径导致的感染中仅略有下降。而三种暴露途径导致的感染对小鼠其他组织中人CD4^(+)T淋巴细胞的影响则略有不同:阴道暴露使阴道中的CD4^(+)T淋巴细胞明显下降,而对其他组织中的人CD4^(+)T淋巴细胞无影响;静脉和直肠暴露对各组织中人CD4^(+)T淋巴细胞水平的影响不大。结论SIVgor能通过静脉、直肠和阴道途径感染人源化小鼠并在其内高效复制。黏膜相关淋巴组织中SIVgor对CD4^(+)T淋巴细胞的选择性细胞毒性与人类HIV-1感染相似。由于人类仍可因狩猎暴露于SIVs,新的人畜共患病可能再次发生。因此,建立能评估当前和未来人畜共患病的模型系统至关重要。

Objective Western gorillas(Gorilla gorilla gorilla) are the natural hosts of simian immunodeficiency virusgorilla(SIVgor).The primary objective of our study is to determine whether SIVgor is capable of being transmitted to and replicating in humans.Method Human hematopoietic stem cells were transplanted into immune-deficient mice via tail veil dose to make the humanized mice reconstituted with a complete human hematopoietic system.Through determining HIV viral loads and CD4^(+)T cell levels in humanized mice,the capacity of SIVgor to be transmitted after intravenous and mucosal exposure,to replicate in vivo and to kill CD4^(+)T cells were evaluated.Result After intravenous exposure,SIVgor replicated very efficiently in humanized mice reaching viral loads comparable to HIV infected humans.In addition,humanized mice were susceptible to SIVgor infection after mucosal exposure.Both rectal and vaginal inoculation led to disseminated infection.However,despite high levels of virus replication these infections resulted in only a modest reduction in the levels of human CD4^(+)T cells in the peripheral blood of humanized mice.However,effects of SIVgor infection on human CD4^(+)T cells in other tissues except blood via three exposure routes were slightly different:CD4^(+)T cells in the vagina decreased significantly after vaginal exposure while those in other tissues were preserved;after venous and rectal exposure human CD4^(+)T cells in all the studied tissues were rarely affected.Conclusion SIVgor was able to infect humanized mice via both intravenous and mucosal routes and then replicate efficiently in the infected animals.Selective cytotoxicity for CD4^(+)T cells in mucosal associated lymphoid tissues recapitulated HIV-1 infection of humans.Since humans are still exposed to SIVs from bushmeat,new zoonoses are likely to occur.Therefore,it is critical to establish model systems that can evaluate present and future dangers.