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恒河猴对重复低剂量直肠内接种SHIVSF162P3攻击的易感性与TRIM5基因型无关。

Susceptibility to repeated, low-dose, rectal SHIVSF162P3 challenge is independent of TRIM5 genotype in rhesus macaques.

作者信息

Butler Katherine, Morgan Jennifer S, Hanson Debra L, Adams Debra, Garcia-Lerma J Gerardo, Heneine Walid, Ellenberger Dennis, Hendry R Michael, McNicholl Janet, Johnson Welkin E, Kersh Ellen N

机构信息

Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

出版信息

AIDS Res Hum Retroviruses. 2013 Jul;29(7):1091-4. doi: 10.1089/aid.2012.0383. Epub 2013 Mar 29.

Abstract

Infections following repeated, low-dose (RLD), mucal S(H)IV exposures of macaques are used to model sexual HIV exposures for biomedical prevention testing. Different susceptibilities among animals can complicate study designs. In rhesus macaques, TRIM5 alleles Q, CypA, and TFP are resistance factors for infection with some S(H)IV strains, but not for SIVmac239 due to its capsid properties. SIVmac239-derived SHIVSF162P3 has been demonstrated to reproducibly infect mucosally in vaginal and rectal RLD models. To further test the suitability of SHIVSF162P3 for RLD models, we studied the influence of the TRIM5 genotype on susceptibility to rectal RLD infection and on plasma viremia by analyzing 43 male Indian rhesus macaques from control arms of completed studies. The median number of exposures required for infection was three (Q/Q, n=4) (TRIM5 alleles, number of macaques, respectively), four (Q/CypA, n=7), three (TFP/Q, n=15), three (TFP/TFP, n=15), and two (TFP/CypA, n=2); TRIM5(CypA/CypA) was not represented in our study. Median peak viremia (log10 viral copies/ml) in infected animals was 7.4 (Q/Q, n=4), 7.2 (Q/CypA, n=6), 7.3 (TFP/Q, n=13), 7.1 (TFP/TFP, n=15), and 6.5 (TFP/CypA; n=2). Neither susceptibility nor peak viremia was significantly different (log rank test, Kruskal-Wallis test, respectively). Rhesus macaques' susceptibility to RLD SHIVSF162P3 is independent of the TRIM5 TFP, CypA, and Q alleles, with the limitation that the power to detect any impact of CypA/CypA and TFP/CypA genotypes was nonexistent or low, due to absence or infrequency, respectively. The finding that TRIM5 alleles do not restrict mucosal infection or ensuing replication rates suggests that SHIVSF162P3 is indeed suitable for RLD experimentation.

摘要

恒河猴经反复低剂量(RLD)黏膜暴露于猿猴-人免疫缺陷病毒(S(H)IV)后发生的感染,被用于模拟艾滋病病毒(HIV)性暴露,以进行生物医学预防试验。动物之间不同的易感性会使研究设计复杂化。在恒河猴中,TRIM5等位基因Q、环孢素A(CypA)和TFP是对某些S(H)IV毒株感染的抗性因素,但对SIVmac239不具有抗性,这归因于其衣壳特性。源自SIVmac239的猿猴-人免疫缺陷病毒(SHIV)SF162P3已被证明在阴道和直肠RLD模型中可重复性地感染黏膜。为了进一步测试SHIVSF162P3在RLD模型中的适用性,我们通过分析来自已完成研究对照组的43只雄性印度恒河猴,研究了TRIM5基因型对直肠RLD感染易感性和血浆病毒血症的影响。感染所需的暴露次数中位数为3次(Q/Q,n = 4)(TRIM5等位基因,分别为猕猴数量),4次(Q/CypA,n = 7),3次(TFP/Q,n = 15),3次(TFP/TFP,n = 15),以及2次(TFP/CypA,n = 2);我们的研究中未出现TRIM5(CypA/CypA)。感染动物的病毒血症峰值中位数(log10病毒拷贝数/毫升)为7.4(Q/Q,n = 4),7.2(Q/CypA,n = 6),7.3(TFP/Q,n = 13),7.1(TFP/TFP,n = 15),以及6.5(TFP/CypA;n = 2)。易感性和病毒血症峰值均无显著差异(分别为对数秩检验、Kruskal-Wallis检验)。恒河猴对RLD SHIVSF162P3的易感性独立于TRIM5的TFP、CypA和Q等位基因,局限性在于由于分别不存在或频率低,检测CypA/CypA和TFP/CypA基因型任何影响的效能不存在或很低。TRIM5等位基因不限制黏膜感染或后续复制率这一发现表明,SHIVSF

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