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Analyses of Mitochondrial DNA and Immune Phenotyping Suggest Accelerated T-Cell Turnover in Treated HIV.

ABSTRACT: BACKGROUND:HIV infection is associated with premature aging, and mitochondrial integrity is compromised during the aging process. Because mitochondrial toxicity is a consequence of antiretroviral therapies (ARTs), we hypothesized HIV and long-term ART would correlate with immunosenescence and mitochondrial DNA (mtDNA) pathology. SETTING:Thirteen older HIV-infected individuals (aged >40 years) with virologic suppression (stratified by duration of ART) were compared with 10 uninfected controls well-matched for age. METHODS:Peripheral blood T-cells were immunophenotyped to measure immune activation, proliferation, and immunosenescence in subsets. mtDNA copies per cell and the relative abundance of mtDNA carrying the "common deletion" (RACD) were quantified by droplet digital polymerase chain reaction. RESULTS:Immune activation was higher in HIV-infected individuals than HIV-uninfected individuals in mature CD4 T-cell subsets (CD4TTM P = 0.025, CD4TEM P = 0.0020) regardless of ART duration. Cell populations from uninfected individuals were more likely to be more senescent populations in mature CD4 T-cell subsets (TTM P = 0.017), and CD8 (CD8TEMRA+ P = 0.0026). No differences were observed in mtDNA or RACD levels in any CD4 T-cell subsets, while CD8TSCM of infected individuals trended to have more mtDNA (P = 0.057) and reduced RACD (P = 0.0025). CONCLUSIONS:HIV-infected individuals demonstrated increased immune activation, but reduced senescence in more mature T-cell subsets. Increased mtDNA content and lower RACD in CD8TSCM suggest immune activation driven turnover of these cells in HIV-infected persons.

SUBMITTER: Massanella M

PROVIDER: S-EPMC6650285 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Analyses of Mitochondrial DNA and Immune Phenotyping Suggest Accelerated T-Cell Turnover in Treated HIV.

Massanella Marta M Karris Maile Y MY Pérez-Santiago Josué J Yek Christina C Vitomirov Andrej A Mehta Sanjay R SR

Journal of acquired immune deficiency syndromes (1999) 20181101 3

<h4>Background</h4>HIV infection is associated with premature aging, and mitochondrial integrity is compromised during the aging process. Because mitochondrial toxicity is a consequence of antiretroviral therapies (ARTs), we hypothesized HIV and long-term ART would correlate with immunosenescence and mitochondrial DNA (mtDNA) pathology.<h4>Setting</h4>Thirteen older HIV-infected individuals (aged >40 years) with virologic suppression (stratified by duration of ART) were compared with 10 uninfect ...[more]

PMID: 30312276

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Project description:BACKGROUND:The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found in primates. METHODS AND FINDINGS:We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of Trichuris recovered from a human and a porcine host in China and from a françois' leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively) suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from Trichuris from françois' leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related. CONCLUSION AND SIGNIFICANCE:Our results indicate that Trichuris species infecting humans and pigs are phylogenetically distinct across geographical regions, which might have important implications for the implementation of suitable and effective control strategies in different regions. Moreover, we provide support for the hypothesis that Trichuris infecting primates represents a complex of cryptic species with some species being able to infect both humans and non-human primates.

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Analyses of Mitochondrial DNA and Immune Phenotyping Suggest Accelerated T-Cell Turnover in Treated HIV.

Publications

Analyses of Mitochondrial DNA and Immune Phenotyping Suggest Accelerated T-Cell Turnover in Treated HIV.

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