Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.
Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.
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DOI：
10.1371/journal.pone.0056527
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Harding CV
中科院分区：
文献类型：
--
作者：
Hardy GA;Sieg S;Rodriguez B;Anthony D;Asaad R;Jiang W;Mudd J;Schacker T;Funderburg NT;Pilch-Cooper HA;Debernardo R;Rabin RL;Lederman MM;Harding CV
I型干扰素(IFN-I)越来越多地参与HIV-1的发病机制。多项研究表明，在HIV-1感染过程中，干扰素-I水平升高以及干扰素-I诱导的基因和蛋白质表达特征，然而，干扰素-I水平升高的种类尚未确定，其来源尚不清楚，其在推动HIV-1致病机制中的作用也存在争议。我们用ELISAs和生物法鉴定血浆中干扰素-I的种类，并用qRT-PCR方法调查血液和淋巴结组织中干扰素-I的潜在来源。此外，我们还测量了丙型肝炎病毒感染者治疗性应用干扰素α的效果，以模拟干扰素α对慢性免疫激活的影响。未经治疗的HIV-1感染者血浆中干扰素-I生物活性显著高于非感染者(p = 0.012)，干扰素α是与干扰素-I生物活性相关的主要干扰素亚型(r = 0.658，p<；0.001)。在接受抗逆转录病毒治疗的受试者血浆中未检测到干扰素α。在未经治疗的慢性α感染中，干扰素α的表达仅限于淋巴组织细胞，提示外周血白细胞不是干扰素DNA的主要来源。血浆干扰素-I水平与CD4T细胞计数呈负相关(p = 0.003)，与血浆HIV-1RNA和CD8T细胞CD38RNA表达水平呈正相关(p = 0.009)。在丙型肝炎病毒感染者中，干扰素-I和利巴韦林治疗增加了CD8T细胞上CD38CD38的表达(p = 0.003)。这些研究确定，来自淋巴结的干扰素α，而不是血液中的白细胞，可能是干扰素-I签名的一个来源，这种签名有助于在艾滋病毒-1感染中激活免疫。
Type-I interferon (IFN-I) has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFNα in HCV-infected subjects to model the effect of IFNα on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p = 0.012), and IFNα was the predominant IFN-I subtype correlating with IFN-I bioactivity (r = 0.658, p<0.001). IFNα was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFNα mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFNα in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p = 0.003) and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p = 0.009). In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p = 0.003). These studies identify IFNα derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection.
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DOI：
10.1073/pnas.0600363103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Herbeuval, JP;Nilsson, J;Shearer, GM
通讯作者：
Shearer, GM
DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Honda, K;Sakaguchi, S;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
15.9
作者：
Beignon, AS;McKenna, K;Bhardwaj, N
通讯作者：
Bhardwaj, N
影响因子：
5.4
作者：
Fonteneau, JF;Larsson, M;Bhardwaj, N
通讯作者：
Bhardwaj, N
影响因子：
2.7
作者：
Kadowaki, N;Liu, YJ
通讯作者：
Liu, YJ