Sivanandham Sindhuja, Sivanandham Ranjit, Xu Cuiling, Symmonds Jen, Sette Paola, He Tianyu, Funderburg Nicholas, Abdel-Mohsen Mohamed, Landay Alan, Apetrei Cristian, Pandrea Ivona
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Front Immunol. 2025 Mar 10;16:1475160. doi: 10.3389/fimmu.2025.1475160. eCollection 2025.
Lipid profiles change in human immunodeficiency virus (HIV) infection and correlate with inflammation. Lipidomic alterations are impacted by multiple non-HIV-related behavioral risk factors; thus, use of animal models in which these behavioral factors are controlled may inform on the specific lipid changes induced by simian immunodeficiency virus (SIV) infection and/or antiretroviral therapy (ART).
Using ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy, we assessed and compared (ANOVA) longitudinal lipid changes in naïve and ART-treated SIV-infected pigtailed macaques (PTMs). Key parameters of infection (IL-6, TNFa, D-dimer, CRP and CD4 T cell counts) were correlated (Spearman) with lipid concentrations at critical time points of infection and treatment.
Sphingomyelins (SM) and lactosylceramides (LCER) increased during acute infection, returning to baseline during chronic infection; Hexosylceramides (HCER) increased throughout infection, being normalized with prolonged ART; Phosphatidylinositols (PI) and lysophosphatidylcholines (LPC) decreased with SIV infection and did not return to normal with ART; Phosphatidylethanolamines (PE), lysophosphatidylethanolamines (LPE) and phosphatidylcholines (PC) were unchanged by SIV infection, yet significantly decreased throughout ART. Specific lipid species (SLS) were also substantially modified by SIV and/or ART in most lipid classes. In conclusion, using a metabolically controlled model, we identified specific lipidomics signatures of SIV infection and/or ART, some of which were similar to people living with HIV (PWH). Many SLS were identical to those involved in development of organ dysfunctions encountered in virally suppressed individuals. Lipid changes also correlated with markers of disease progression, inflammation and coagulation.
Our data suggest that lipidomic profile alterations contribute to residual systemic inflammation and comorbidities seen in HIV/SIV infections and therefore may be used as biomarkers of SIV/HIV comorbidities. Further exploration into the benefits of interventions targeting dyslipidemia is needed for the prevention HIV-related comorbidities.
人类免疫缺陷病毒（HIV）感染会导致血脂谱发生变化，并与炎症相关。脂质组学改变受到多种与HIV无关的行为危险因素的影响；因此，使用能够控制这些行为因素的动物模型，可能有助于了解猿猴免疫缺陷病毒（SIV）感染和/或抗逆转录病毒疗法（ART）所引起的特定脂质变化。
我们使用超高效液相色谱-串联质谱法，评估并比较了（方差分析）未感染SIV和接受ART治疗的感染SIV的猪尾猕猴（PTM）的纵向脂质变化。在感染和治疗的关键时间点，将感染的关键参数（白细胞介素-6、肿瘤坏死因子α、D-二聚体、C反应蛋白和CD4 T细胞计数）与脂质浓度进行相关性分析（斯皮尔曼相关性分析）。
鞘磷脂（SM）和乳糖神经酰胺（LCER）在急性感染期间增加，在慢性感染期间恢复至基线水平；己糖神经酰胺（HCER）在整个感染过程中增加，随着ART疗程延长恢复正常；磷脂酰肌醇（PI）和溶血磷脂酰胆碱（LPC）在SIV感染时减少，且接受ART治疗后未恢复正常；磷脂酰乙醇胺（PE）、溶血磷脂酰乙醇胺（LPE）和磷脂酰胆碱（PC）在SIV感染时未发生变化，但在整个ART治疗过程中显著减少。大多数脂质类别中的特定脂质种类（SLS）也受到SIV和/或ART的显著影响。总之，通过使用代谢受控模型，我们确定了SIV感染和/或ART的特定脂质组学特征，其中一些与HIV感染者（PWH）相似。许多SLS与病毒抑制个体中出现的器官功能障碍发展有关。脂质变化也与疾病进展、炎症和凝血标志物相关。
我们的数据表明，脂质组学谱的改变导致了HIV/SIV感染中残留的全身炎症和合并症，因此可用作SIV/HIV合并症的生物标志物。需要进一步探索针对血脂异常干预措施的益处，以预防与HIV相关的合并症。
