Examining Relationships between Metabolism and Persistent Inflammation in HIV Patients on Antiretroviral Therapy

Ahmed, Duale; Roy, David; Cassol, Edana

doi:10.1155/2018/6238978

Cited by 46 publications

(45 citation statements)

References 211 publications

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“…HIV-1 selectively infects CD4 T cells with high levels of oxidative phosphorylation and glycolysis, independently of their activation phenotype. In a similar way to carcinogenesis, it is also now admitted the existence of a metabolic reprogramming upon HIV infection, related to modifications in glucose metabolism (Ahmed et al, 2018).…”

Section: Metabolic Reprogramming Of Immune Cells In Atmentioning

confidence: 97%

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

et al. 2019

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Although white AT can contribute to anti-infectious immune responses, it can also be targeted and perturbed by pathogens. The AT's immune involvement is primarily due to strong pro-inflammatory responses (with both local and paracrine effects), and the large number of fat-resident macrophages. Adipocytes also exert direct antimicrobial responses. In recent years, it has been found that memory T cells accumulate in AT, where they provide efficient secondary responses against viral pathogens. These observations have prompted researchers to re-evaluate the links between obesity and susceptibility to infections. In contrast, AT serves as a reservoir for several persistence pathogens, such as human adenovirus Ad-36, Trypanosoma gondii, Mycobacterium tuberculosis, influenza A virus, and cytomegalovirus (CMV). The presence and persistence of bacterial DNA in AT has led to the concept of a tissuespecific microbiota. The unexpected coexistence of immune cells and pathogens within the specific AT environment is intriguing, and its impact on anti-infectious immune responses requires further evaluation. AT has been recently identified as a site of HIV persistence. In the context of HIV infection, AT is targeted by both the virus and the antiretroviral drugs. AT's intrinsic metabolic features, large overall mass, and wide distribution make it a major tissue reservoir, and one that may contribute to the pathophysiology of chronic HIV infections. Here, we review the immune, metabolic, viral, and pharmacological aspects that contribute to HIV persistence in AT. We also evaluate the respective impacts of both intrinsic and HIV-induced factors on AT's involvement as a viral reservoir. Lastly, we examine the potential consequences of HIV persistence on the metabolic and immune activities of AT.

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Section: Metabolic Reprogramming Of Immune Cells In Atmentioning

confidence: 97%

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

et al. 2019

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“…The use of ART to control HIV-1 has been associated with a number of cellular changes [44][45][46][47]. Since EpKS patients in our cohort had varying ART duration and some with detectable plasma HIV-1 viral load despite ART treatment, we tested the effect of ART duration and HIV-1 viremia on EpKS transcriptome profiles.…”

Section: Plos Pathogensmentioning

confidence: 99%

“…Whether the same dysregulations, or similar magnitude of changes, occur in EnKS, has not been investigated. Because lipid metabolic dysregulation is common in ART treated HIV-1 infected individuals [44][45][46][47], it will be important to determine whether the KS-associated lipid metabolism defects are due to KSHV infection, attributable to HIV-1 co-infection or result from ART. Moreover, a male gender bias in KS has been noted, especially for classical and EnKS, suggesting a potential involvement of androgens or androgen receptors in the disease pathogenesis [48][49][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

Comparative transcriptome analysis of endemic and epidemic Kaposi’s sarcoma (KS) lesions and the secondary role of HIV-1 in KS pathogenesis

et al. 2020

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In sub-Saharan Africa, endemic Kaposi's sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi's sarcoma (EpKS) resulting from the ongoing HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ARTtreated and-naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs-naïve EpKS and male vs female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r = 0.83, p<10 −10). A subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude, but not unique dysregulation in EnKS compared to EpKS. While gender and ART had no detectable contribution, the trend toward higher magnitude of gene dysregulation in EnKS coupled with

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“…Therefore, it has been observed that there is a growing concern among patients with T2D to find the right line of treatment when they find themselves as HIV positive. Since T2D is associated with many other complications, treating these patients with the right combination of cART needs more collaborative approaches among clinicians in order to avoid multiorgans related complications [94,95].…”

Section: Prevalence and Incidence Rates Of T2d In The Rio Grande Valleymentioning

confidence: 99%

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley

Garza

Rodrigo

Fernandez

et al. 2020

CHR

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: The Human Immunodeficiency Virus (HIV-1) infection remains a persistent predicament for the State of Texas, ranking seventh among the most documented HIV cases in the United States. In this regard, the Rio Grande Valley (RGV) in South Texas is considered as one of the least investigated areas of the state with respect to HIV infection and HIV associated comorbidities. Considering the 115% increase in average HIV incidence rates per 100,000 within the RGV from 2007-2015, it is worth characterizing this population with respect to their HIV-1 infection, HIV-1 Associated Neurocognitive Disorders (HAND), and the association of treatment with combined antiretroviral therapy (cART). Moreover, the increased rate of Type-2 Diabetes (T2D) in the RGV population is intertwined with that of HIV-1 infection facing challenges due to the lack of knowledge about prevention to inadequate access to healthcare. Hence, the role of T2D in the development of HAND among the people living with HIV (PLWH) in the RGV will be reviewed to establish a closer link between T2D and HAND in cART-treated patients of the RGV.

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Examining Relationships between Metabolism and Persistent Inflammation in HIV Patients on Antiretroviral Therapy

Cited by 46 publications

References 211 publications

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

Comparative transcriptome analysis of endemic and epidemic Kaposi’s sarcoma (KS) lesions and the secondary role of HIV-1 in KS pathogenesis

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley

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