Metabolomics in HIV Infection
Acquired immunodeficiency syndrome (AIDS), a chronic and life-threatening condition caused by the infection of human immunodeficiency virus (HIV), remains a global health problem. Since HIV infection has a profound effect on cell metabolism, which plays an important role in the pathogenesis and progression of HIV disease. Nowadays, metabolomics has become a versatile tool in HIV research.
Human immunodeficiency virus (HIV)
Since the beginning of this epidemic, HIV has infected more than 70 million people. To date, despite the lack of a cure, substantial progress has been made in HIV diagnosis and treatment. With treatments such as antiretroviral therapy (ART), infected individuals can survive chronic infections. HIV can be divided into two types, including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). HIV-1, which is responsible for the majority of AIDS cases worldwide, is more virulent and transmissible than HIV-2. After infection, HIV viral load peaks about two weeks later at an excess of 1 million copies of HIV RNA per milliliter. Following acute and primary infections, there is an asymptomatic phase that can last for many years before symptoms appear and disease progresses. However, during the asymptomatic stage, HIV can still infect the cells and replicate within cells, resulting in a decrease in CD4+ T cells.
Application of metabolomics to HIV
Metabolomics studies regarding HIV have attempted to identify metabolic biomarkers from various biological fluids, including plasma, oral lavage, and bronchoalveolar lavage fluid (BALF). These metabolic biomarkers can greatly facilitate the diagnosis of HIV-related diseases and the development of HIV treatment.
Metabolic biomarkers for HIV infection/response to antiretroviral (ART) treatment
Initial efforts showed that the comparison of serum metabolic profiles of patients can be applied to identify HIV+ and HIV−. In addition, metabolomics studies using the H-NMR method revealed the discrimination between ART-treated/ART-naïve HIV+ patients and HIV- controls, which was based on changes in glucose, lipid, glycerol, choline, and amino acid levels. The technique appears to have the potential diagnostic capabilities that could replace western blot (WB), the current gold standard.
Identify metabolic biomarkers to develop fast and non-invasive HIV diagnostic tests
Using GC-MS and LC-MS methods, researchers had studied the metabolic profiles of oral lavage form ART-naïve, ART-experienced patients and healthy ones. Hopefully, there was an increased phenylalanine/tyrosine ratio in ART-naïve patients, opening doors for new oral biomarkers. Besides, due to secondary lung infections that are common in HIV+ patients, researchers used LC-MS to investigate the discrimination between metabolic profiles of bronchoalveolar lavage fluid (BALF) of HIV+ and controls. The results showed that the groups clustered in orthogonal PLS-DA (OPLS-DA) models and there were significant alternations in phospholipids, tripeptides, and pyochelin levels.
Identify metabolite markers correlating to HIV-induced oxidative stress (OS)
To identify metabolite markers correlating to HIV-induced oxidative stress, metabolomics studies (untargeted and targeted metabolomics) have been employed to explore multiple biofluids, such as urine, serum, and whole blood. Among them, amino acid metabolism has been studied, including alanine, tryptophan, and glutamine.
Explore the pathogenicity of HIV
To study the factor responsible for the lower pathogenicity of HIV-2, the LC/MS method has been used to investigate the difference of metabolic profiles in HIV-1 and HIV-2 infections. Their glycolytic and TCA profiles were similar, while the HIV-2 profile showed an increase in deoxynucleotide triphosphate (dNTPs). Additionally, using LC-MS/MS, the metabolites of HIV-infected and noninfected primary monocyte-derived macrophages were studied. HIV-1 infections were discovered with increased glycolysis intermediates, including glyceraldehyde 3-phosphate (G3P) and fructose 1,6-bisphosphate (FBP), and HIV-2 strains were characterized by an increase in quinolinate.
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Reference
- Tounta, V., et al. (2021). "Metabolomics in infectious diseases and drug discovery." Molecular Omics, 17(3), 376-393.
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