Myocarditis in CD8-depleted SIV-infected rhesus macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors.
Myocarditis in CD8-depleted SIV-infected rhesus macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors.
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DOI：
10.1371/journal.pone.0014429
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发表时间：
2010-12-23
期刊：
影响因子：
3.7
通讯作者：
O'Neil SP
中科院分区：
文献类型：
--
作者：
Annamalai L;Westmoreland SV;Domingues HG;Walsh DG;Gonzalez RG;O'Neil SP
尽管高效抗逆转录病毒治疗（HAART）已显著降低了与HIV感染相关的发病率和死亡率，但仍有许多抗逆转录病毒毒性被描述，包括使用核苷酸和核苷逆转录酶抑制剂（NRTI）引起的心肌毒性。目前的治疗指南建议使用HAART方案包含两个NRTIs的HIV-1阳性个体的初始治疗;然而，尚未解决由多种NRTIs治疗引起的潜在心脏毒性。我们检查了12只去除CD 8淋巴细胞的成年恒河猴的心肌组织，其中8只动物感染了猿猴免疫缺陷病毒，其中4只接受了由两种NRTI [（9-R-2-膦酰甲氧基丙基腺嘌呤）（PMPA）和（+/−）-β-2 ′，3 ′-双脱氧-5-氟-3 ′-硫代胞苷（RCV）]组成的联合抗逆转录病毒治疗（CART）28天。在所有接受CART的猕猴的心肌中均存在单核炎性细胞的多灶性浸润，但未接受治疗的SIV阳性动物或SIV阴性对照组均不存在。巨噬细胞是病变内的主要炎性细胞，如巨噬细胞标志物Iba 1和CD 68的免疫反应性所示。接受CART的猴心脏标本的病毒负荷显著低于未治疗动物（p<0.05），但TNF-α mRNA的量显著高于SIV阳性未治疗动物或未感染对照组（p<0.05）。干扰素-γ（IFN-γ），IL-1β和CXCL 11 mRNA在SIV阳性猴的心脏组织中上调，与抗逆转录病毒治疗无关，但CXCL 9 mRNA仅在接受CART的猕猴的心脏组织中上调。这些结果表明，短期治疗与多种NRTI可能与心肌炎，并证明CD 8-耗尽SIV阳性恒河猴是一个有用的模型，用于研究联合抗逆转录病毒治疗的心脏毒性作用，在设置免疫缺陷病毒感染。
Although highly active antiretroviral therapy (HAART) has dramatically reduced the morbidity and mortality associated with HIV infection, a number of antiretroviral toxicities have been described, including myocardial toxicity resulting from the use of nucleotide and nucleoside reverse transcriptase inhibitors (NRTIs). Current treatment guidelines recommend the use of HAART regimens containing two NRTIs for initial therapy of HIV-1 positive individuals; however, potential cardiotoxicity resulting from treatment with multiple NRTIs has not been addressed. We examined myocardial tissue from twelve CD8 lymphocyte-depleted adult rhesus macaques, including eight animals infected with simian immunodeficiency virus, four of which received combined antiretroviral therapy (CART) consisting of two NRTIs [(9-R-2-Phosphonomethoxypropyl Adenine) (PMPA) and (+/−)-beta-2′,3′-dideoxy-5-fluoro-3′-thiacytidine (RCV)] for 28 days. Multifocal infiltrates of mononuclear inflammatory cells were present in the myocardium of all macaques that received CART, but not untreated SIV-positive animals or SIV-negative controls. Macrophages were the predominant inflammatory cells within lesions, as shown by immunoreactivity for the macrophage markers Iba1 and CD68. Heart specimens from monkeys that received CART had significantly lower virus burdens than untreated animals (p<0.05), but significantly greater quantities of TNF-α mRNA than either SIV-positive untreated animals or uninfected controls (p<0.05). Interferon-γ (IFN-γ), IL-1β and CXCL11 mRNA were upregulated in heart tissue from SIV-positive monkeys, independent of antiretroviral treatment, but CXCL9 mRNA was only upregulated in heart tissue from macaques that received CART. These results suggest that short-term treatment with multiple NRTIs may be associated with myocarditis, and demonstrate that the CD8-depleted SIV-positive rhesus monkey is a useful model for studying the cardiotoxic effects of combined antiretroviral therapy in the setting of immunodeficiency virus infection.
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影响因子：
5.8
作者：
Bilate, Angelina M. B.;Salemi, Vera M.;Cunha-Neto, Edecio
通讯作者：
Cunha-Neto, Edecio
影响因子：
158.5
作者：
Bozzette, SA;Ake, CF;Louis, TA
通讯作者：
Louis, TA
DOI：
10.1016/0735-1097(88)90420-2
发表时间：
1988-08-01
影响因子：
24
作者：
BAROLDI, G;CORALLO, S;NEGRI, C
通讯作者：
NEGRI, C
影响因子：
168.9
作者：
Habib, FM;Springall, DR;Polak, JM
通讯作者：
Polak, JM
DOI：
10.1111/j.1749-6632.2001.tb03912.x
发表时间：
2001-01-01
期刊：
HIV-ASSOCIATED CARDIOVASCULAR DISEASE: CLINICAL AND BIOLOGICAL INSIGHTS
影响因子：
--
作者：
Fantoni, M;Autore, C;Del Borgo, C
通讯作者：
Del Borgo, C