Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy.
Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy.
复制标题
响应HIV感染的免疫代谢重编程未通过抑制性抗逆转录病毒疗法完全归一化。
DOI：
10.3390/v14061313
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发表时间：
2022-06-15
期刊：
影响因子：
--
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中科院分区：
文献类型：
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背景：HIV感染导致免疫代谢重编程。虽然我们开始了解这种代谢重编程如何调节对HIV感染的免疫反应，但我们目前还不了解ART对HIV感染者（PWH）免疫代谢的影响。研究方法：本研究使用了来自Rakai Uganda的HIV感染者（n = 278）和地理位置匹配的HIV血清阴性对照受试者（n = 300）的血清。在开始抗逆转录病毒疗法前和开始抗逆转录病毒疗法后约2年，从HIV感染者中获得血清。我们对血清进行了代谢组学分析，并将我们的分析集中在与免疫代谢相关的代谢底物和途径上。结果如下：HIV感染与代谢适应相关，包括糖酵解过度活跃、乳酸形成增加、戊糖磷酸途径（PPP）活性增加、长链脂肪酸β-氧化减少、中链脂肪酸利用增加和氨基酸催化剂增加。ART后，酮体、肉毒碱和氨基酸代谢的血清水平恢复正常，但糖酵解、PPP、乳酸产生和长链脂肪酸的β-氧化仍异常。结论：我们的研究结果表明，HIV感染与增加的免疫代谢需求有关，这种需求通过利用替代的能量底物（包括脂肪酸和氨基酸）得到满足。单独的ART不足以完全恢复HIV感染的代谢重编程，这表明免疫代谢的持续损害可能导致病毒抑制的PWH中的慢性免疫激活和共病。
Background: HIV infection results in immunometabolic reprogramming. While we are beginning to understand how this metabolic reprogramming regulates the immune response to HIV infection, we do not currently understand the impact of ART on immunometabolism in people with HIV (PWH). Methods: Serum obtained from HIV-infected (n = 278) and geographically matched HIV seronegative control subjects (n = 300) from Rakai Uganda were used in this study. Serum was obtained before and ~2 years following the initiation of ART from HIV-infected individuals. We conducted metabolomics profiling of the serum and focused our analysis on metabolic substrates and pathways assocaited with immunometabolism. Results: HIV infection was associated with metabolic adaptations that implicated hyperactive glycolysis, enhanced formation of lactate, increased activity of the pentose phosphate pathway (PPP), decreased β-oxidation of long-chain fatty acids, increased utilization of medium-chain fatty acids, and enhanced amino acid catabolism. Following ART, serum levels of ketone bodies, carnitine, and amino acid metabolism were normalized, however glycolysis, PPP, lactate production, and β-oxidation of long-chain fatty acids remained abnormal. Conclusion: Our findings suggest that HIV infection is associated with an increased immunometabolic demand that is satisfied through the utilization of alternative energetic substrates, including fatty acids and amino acids. ART alone was insufficient to completely restore this metabolic reprogramming to HIV infection, suggesting that a sustained impairment of immunometabolism may contribute to chronic immune activation and comorbid conditions in virally suppressed PWH.
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影响因子：
1
作者：
Datta PK;Kaminski R;Hu W;Pirrone V;Sullivan NT;Nonnemacher MR;Dampier W;Wigdahl B;Khalili K
通讯作者：
Khalili K
DOI：
10.1161/circheartfailure.113.000521
发表时间：
2013-09-01
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Djoussé L;Benkeser D;Arnold A;Kizer JR;Zieman SJ;Lemaitre RN;Tracy RP;Gottdiener JS;Mozaffarian D;Siscovick DS;Mukamal KJ;Ix JH
通讯作者：
Ix JH
影响因子：
1.5
作者：
Hegedus A;Kavanagh Williamson M;Khan MB;Dias Zeidler J;Da Poian AT;El-Bacha T;Struys EA;Huthoff H
通讯作者：
Huthoff H
影响因子：
6.4
作者：
Cassol, Edana;Malfeld, Susan;Rossouw, Theresa
通讯作者：
Rossouw, Theresa
影响因子：
3.7
作者：
Barrero CA;Datta PK;Sen S;Deshmane S;Amini S;Khalili K;Merali S
通讯作者：
Merali S