APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression.
APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression.
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DOI：
10.1186/1742-4690-6-23
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发表时间：
2009-03-02
期刊：
影响因子：
3.3
通讯作者：
Reyes-Terán G
中科院分区：
文献类型：
--
作者：
Vázquez-Pérez JA;Ormsby CE;Hernández-Juan R;Torres KJ;Reyes-Terán G
APOBEC3G是一种抗逆转录病毒因子，通过诱导G到A突变起作用。在这项研究中，我们检测了未感染HIV-1的个体在其伴侣诊断时和一年后APOBEC3G的表达。然后，我们将这种表达与处于不同疾病阶段的感染个体的表达进行了比较。在三组pbmc中测量APOBEC3G mRNA：无已知HIV感染危险因素的健康对照组（n = 26），暴露于与HIV阳性伴侣发生无保护性行为至少3个月的未感染者（n = 37），以及处于不同疾病阶段的HIV感染患者（n = 45），其中包括8名低HIV病毒载量< 10,000拷贝/mL （LVL）至少3年的患者。此外，我们还获得了患者病毒的env、gag、pol、nef、vif和LTR的序列。暴露的未感染个体比健康对照组表达更高的APOBEC3G（3.86比1.69相对表达单位），并且在HIV诊断和随后治疗的一年后，他们的表达显著下降。感染个体APOBEC3G表达与CD4+ T细胞计数呈正相关（Rho = 0.57, p = 0.00006），与HIV病毒血症呈负相关（Rho = -0.54, p = 0.00004）。G - A突变百分比与APOBEC3G表达呈正相关（Rho = 0.43, p = 0.0226），且LVL患者的比例高于其他患者（IQR为8.27 ~ 9.64比7.06 ~ 8.1,p = 0.0084）。在8个LVLs中，3个具有超突变，4个仅在病毒vif中具有过早终止密码子。结果表明，在没有感染的情况下，暴露于HIV可能会触发pbmc中APOBEC3G的表达。此外，停止暴露或疾病进展与APOBEC3G表达降低有关。
APOBEC3G is an antiretroviral factor that acts by inducing G to A mutations. In this study, we examined the expression of APOBEC3G in uninfected HIV-1 exposed individuals at the time of their partner's diagnosis and one year later. We then compared this expression with that of infected individuals at different disease stages. APOBEC3G mRNA was measured in PBMCs from three groups: healthy controls with no known risk factor to HIV infection (n = 26), exposed uninfected individuals who had unprotected sex with their HIV+ partners for at least 3 months (n = 37), and HIV infected patients at various disease stages (n = 45), including 8 patients with low HIV viral loads < 10,000 copies/mL (LVL) for at least 3 years. Additionally, we obtained sequences from the env, gag, pol, nef, vif and the LTR of the patients' virus. Exposed uninfected individuals expressed higher APOBEC3G than healthy controls (3.86 vs. 1.69 relative expression units), and their expression significantly decreased after a year from the HIV diagnosis and subsequent treatment of their partners. Infected individuals showed a positive correlation (Rho = 0.57, p = 0.00006) of APOBEC3G expression with CD4+ T cell count, and a negative correlation with HIV viremia (Rho = -0.54, p = 0.00004). The percentage of G to A mutations had a positive correlation (Rho = 0.43, p = 0.0226) with APOBEC3G expression, and it was higher in LVL individuals than in the other patients (IQR 8.27 to 9.64 vs. 7.06 to 8.1, p = 0.0084). Out of 8 LVLs, 3 had hypermutations, and 4 had premature stop codons only in viral vif. The results suggest that exposure to HIV may trigger APOBEC3G expression in PBMCs, in the absence of infection. Additionally, cessation of exposure or advanced disease is associated with decreased APOBEC3G expression.
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DOI：
10.1126/science.1161121
发表时间：
2008-09-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Santiago ML;Montano M;Benitez R;Messer RJ;Yonemoto W;Chesebro B;Hasenkrug KJ;Greene WC
通讯作者：
Greene WC
影响因子：
5.4
作者：
Kao, S;Khan, MA;Strebel, M
通讯作者：
Strebel, M
影响因子：
64.8
作者：
Sheehy, AM;Gaddis, NC;Malim, MH
通讯作者：
Malim, MH
影响因子：
5.4
作者：
Guo, Fei;Cen, Shan;Kleiman, Lawrence
通讯作者：
Kleiman, Lawrence
影响因子：
3.3
作者：
Jin X;Wu H;Smith H
通讯作者：
Smith H