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Article ; Online: SARS-CoV-2 and the host-immune response.

Maison, David P / Deng, Youping / Gerschenson, Mariana

2023 Volume 14, Page(s) 1195871

Abstract: The SARS-CoV-2 pandemic and the COVID-19 disease have affected everyone globally, leading to one of recorded history's most significant research surges. As our knowledge evolves, our approaches to the virus and treatments must also evolve. The evaluation ...

Abstract	The SARS-CoV-2 pandemic and the COVID-19 disease have affected everyone globally, leading to one of recorded history's most significant research surges. As our knowledge evolves, our approaches to the virus and treatments must also evolve. The evaluation of future research approaches to SARS-CoV-2 will necessitate reviewing the host immune response and viral antagonism of that response. This review provides an overview of the current knowledge on SARS-CoV-2 by summarizing the virus and human response. The focuses are on the viral genome, replication cycle, host immune activation, response, signaling, and antagonism. To effectively fight the pandemic, efforts must focus on the current state of research to help develop treatments and prepare for future outbreaks.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Immunity, Innate ; Genome, Viral
Language	English
Publishing date	2023-06-19
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1195871
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Article ; Online: Altered mitochondrial respiration in peripheral blood mononuclear cells of post-acute sequelae of SARS-CoV-2 infection.

Dirajlal-Fargo, Sahera / Maison, David P / Durieux, Jared C / Andrukhiv, Anastasia / Funderburg, Nicholas / Ailstock, Kate / Gerschenson, Mariana / Mccomsey, Grace A

Mitochondrion

2024 Volume 75, Page(s) 101849

Abstract: Peripheral blood mononuclear cells (PBMC) mitochondrial respiration was measured ex vivo from participants without a history of COVID (n = 19), with a history of COVID and full recovery (n = 20), and with PASC (n = 20). Mean mitochondrial basal ... ...

Abstract	Peripheral blood mononuclear cells (PBMC) mitochondrial respiration was measured ex vivo from participants without a history of COVID (n = 19), with a history of COVID and full recovery (n = 20), and with PASC (n = 20). Mean mitochondrial basal respiration, ATP-linked respiration, maximal respiration, spare respiration capacity, ATP-linked respiration, and non-mitochondrial respiration were highest in COVID + PASC+ (p ≤ 0.04). Every unit increase in non-mitochondrial respiration, ATP-linked respiration, basal respiration, spare respiration capacity, and maximal respiration increased the predicted odds of PASC between 1 % and 6 %. Mitochondrial dysfunction in PBMCs may be contributing to the etiology of PASC.
MeSH term(s)	Humans ; Leukocytes, Mononuclear ; Post-Acute COVID-19 Syndrome ; COVID-19 ; SARS-CoV-2 ; Respiration ; Disease Progression ; Adenosine Triphosphate
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2024-02-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2024.101849
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Article ; Online: Novel protective effect of the FOXO3 longevity genotype on mechanisms of cellular aging in Okinawans.

Torigoe, Trevor H / Willcox, D Craig / Shimabukuro, Michio / Higa, Moritake / Gerschenson, Mariana / Andrukhiv, Anastasia / Suzuki, Makoto / Morris, Brian J / Chen, Randi / Gojanovich, Greg S / Allsopp, Richard C / Willcox, Bradley J

npj aging

2024 Volume 10, Issue 1, Page(s) 18

Abstract: The genetic association of FOXO3 genotypes with human longevity is well established, although the mechanism is not fully understood. We now report on the relationship of the FOXO3 longevity variant rs2802292 with telomere length, telomerase activity, ... ...

Abstract	The genetic association of FOXO3 genotypes with human longevity is well established, although the mechanism is not fully understood. We now report on the relationship of the FOXO3 longevity variant rs2802292 with telomere length, telomerase activity, FOXO3 expression, and inflammatory cytokine levels in men and women. In agreement with earlier work, the FOXO3 longevity variant conferred protection against telomere shortening of peripheral blood mononuclear cells from adults aged 55 years and older. This was accompanied by higher levels of telomerase activity in mononuclear cells for carriers of the longevity-associated FOXO3 G-allele of SNP rs2802292 (P = 0.015). FOXO3 mRNA expression increased slightly with age in both young (P = 0.02) and old (P = 0.08) G-allele carriers. Older female G-allele carriers displayed a modest decline in levels of pro-inflammatory cytokine IL-6 with age (P = 0.07). In contrast, older male G-allele carriers displayed an age-dependent increase in levels of anti-inflammatory cytokine IL-10 with age (P = 0.04). Thus, FOXO3 may act through several different pro-longevity mechanisms, which may differ by age and sex.
Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ISSN	2731-6068
ISSN (online)	2731-6068
DOI	10.1038/s41514-024-00142-8
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Article ; Online: Selenoprotein I deficiency in T cells promotes differentiation into tolerant phenotypes while decreasing Th17 pathology.

Ma, Chi / Hoffmann, FuKun W / Nunes, Lance G / Urena, Frank / Andrukhiv, Anastasia / Gerschenson, Mariana / Pitts, Matthew W / Hoffmann, Peter R

Journal of leukocyte biology

2022 Volume 112, Issue 6, Page(s) 1387–1397

Abstract: Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase contributing to cellular metabolism and the synthesis of glycosylphosphatidylinositol (GPI) anchors. SELENOI knockout (KO) in T cells has been shown to impair metabolic reprogramming ... ...

Abstract	Selenoprotein I (SELENOI) is an ethanolamine phospholipid transferase contributing to cellular metabolism and the synthesis of glycosylphosphatidylinositol (GPI) anchors. SELENOI knockout (KO) in T cells has been shown to impair metabolic reprogramming during T cell activation and reduce GPI-anchored Thy-1 levels, which are both crucial for Th17 differentiation. This suggests SELENOI may be important for Th17 differentiation, and we found that SELENOI was indeed up-regulated early during the activation of naïve CD4
MeSH term(s)	Mice ; Animals ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics ; Th17 Cells ; Interleukin-17/metabolism ; Cell Differentiation ; Mice, Knockout ; Forkhead Transcription Factors/metabolism ; Phenotype ; Selenoproteins/metabolism ; Mice, Inbred C57BL
Chemical Substances	Nuclear Receptor Subfamily 1, Group F, Member 3 ; Interleukin-17 ; Forkhead Transcription Factors ; Selenoproteins
Language	English
Publishing date	2022-08-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.1A0122-080R
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Article ; Online: Lower Insulin Sensitivity Through 36 Months of Life With in Utero HIV and Antiretroviral Exposure in Botswana: Results From the Tshilo Dikotla Study.

Jao, Jennifer / Bonner, Lauren B / Dobinda, Katrina / Powis, Kathleen M / Sun, Shan / Legbedze, Justine / Mmasa, Keolebogile N / Makhema, Joseph / Mmalane, Mompati / Kgole, Samuel / Masasa, Gosego / Moyo, Sikhulile / Gerschenson, Mariana / Mohammed, Terence / Abrams, Elaine J / Kurland, Irwin J / Geffner, Mitchell E

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2024

Abstract: Background: There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure.: Methods: The Tshilo Dikotla study enrolled pregnant ... ...

Abstract	Background: There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. Methods: The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. Results: A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. Conclusions: In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciae088
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells.

Kaur, Harpreet / Minchella, Paige / Alvarez-Carbonell, David / Purandare, Neeraja / Nagampalli, Vijay K / Blankenberg, Daniel / Hulgan, Todd / Gerschenson, Mariana / Karn, Jonathan / Aras, Siddhesh / Kallianpur, Asha R

International journal of molecular sciences

2023 Volume 24, Issue 15

Abstract: HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We ... ...

Abstract	HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus and in SH-SY5Y cells after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20-30%, with the most pronounced effects in latently infected HIV+ hμglia and SH-SY5Y cells. Latently HIV-infected hμglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hμglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron-sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hμglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.
MeSH term(s)	Humans ; Microglia/metabolism ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV Infections/metabolism ; Reactive Oxygen Species/metabolism ; Neuroblastoma/metabolism ; Iron/metabolism ; Mitochondria/metabolism ; DNA, Mitochondrial/metabolism
Chemical Substances	Reactive Oxygen Species ; Iron (E1UOL152H7) ; DNA, Mitochondrial
Language	English
Publishing date	2023-07-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241512242
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Article ; Online: Chronic marijuana use moderates the correlations of serum cholesterol with systemic mitochondrial function and fluid cognition.

Panee, Jun / Pomozi, Viola / Franke, Adrian A / Le Saux, Olivier / Gerschenson, Mariana

Mitochondrion

2020 Volume 52, Page(s) 135–143

Abstract: Activating type 1 cannabinoid (CB1) receptor decreases the particle size of high-density lipoprotein (HDL) and inhibits reverse cholesterol transport (RCT). This study examined whether marijuana (MJ) use is associated with changes of RCT, and how the ... ...

Abstract	Activating type 1 cannabinoid (CB1) receptor decreases the particle size of high-density lipoprotein (HDL) and inhibits reverse cholesterol transport (RCT). This study examined whether marijuana (MJ) use is associated with changes of RCT, and how the latter is associated with mitochondrial function and fluid cognition. We recruited 19 chronic MJ users and 20 nonusers with matched age, BMI, sex, ethnicity, and education. We measured their fluid cognition, mitochondrial function (basal and max respiration, ATP production) in peripheral blood mononuclear cells, cholesterol content in serum lipoprotein fractions, enterolactone/creatinine ratio in urine as a marker for dietary polyphenol intake, and lipase activity in serum. We found that higher percentage of large HDL cholesterol (HDL-C) correlated positively, while that of small HDL-C correlated inversely, with mitochondrial function among MJ users, but correlations of the opposite directions were found among nonusers. The concentrations of large and intermediate HDL-C correlated positively with mitochondrial function and fluid cognition among MJ users, but not among nonusers. Both percentage and concentration of large HDL-C correlated positively, while those of small HDL-C correlated inversely, with amounts of daily and lifetime MJ use. In all participants, higher urinary enterolactone/creatinine ratio and lower serum lipase activity were associated with higher large HDL-C/small HDL-C ratio, implying greater RCT. This study suggests that high MJ use may compromise RCT, which is strongly associated with mitochondrial function and fluid cognition among MJ users.
MeSH term(s)	Adult ; Case-Control Studies ; Cholesterol/blood ; Cognition ; Female ; Humans ; Leukocytes, Mononuclear/chemistry ; Lipase/blood ; Male ; Marijuana Use/blood ; Marijuana Use/metabolism ; Marijuana Use/psychology ; Mitochondria/metabolism ; Pilot Projects ; Young Adult
Chemical Substances	Cholesterol (97C5T2UQ7J) ; Lipase (EC 3.1.1.3)
Language	English
Publishing date	2020-03-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2020.03.006
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Article ; Online: Associations Between Microbiota, Mitochondrial Function, and Cognition in Chronic Marijuana Users.

Panee, Jun / Gerschenson, Mariana / Chang, Linda

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2017 Volume 13, Issue 1, Page(s) 113–122

Abstract: Marijuana (MJ) use is associated with cognitive deficits. Both mitochondrial (mt) dysfunction and gut dysbiosis also affect cognition. We examined whether cognition is related to peripheral blood mononuclear cells' (PBMCs) mt function and fecal ... ...

Abstract	Marijuana (MJ) use is associated with cognitive deficits. Both mitochondrial (mt) dysfunction and gut dysbiosis also affect cognition. We examined whether cognition is related to peripheral blood mononuclear cells' (PBMCs) mt function and fecal microbiota in chronic MJ users. Nineteen chronic MJ users and 20 non-users were evaluated using the Cognition Battery in NIH Toolbox, their mt function for ATP production, and basal and maximal respirations were measured in PBMCs using the Seahorse XFe96 Analyzer, and the abundances of Prevotella and Bacteroides (associated with plant-based and animal product-based diet, respectively) were calculated from stool microbiota analysis. Average Prevotella:Bacteroides ratio was ~13-fold higher in nonusers than users. Lifetime MJ use correlated inversely with Prevotella:Bacteroides ratio (p = 0.05), mt function (p = 0.0027-0.0057), and Flanker Inhibitory Control and Attention (p = 0.041). Prevotella abundance correlated positively, while Bacteroides abundance correlated inversely, with mt function across all participants (p = 0.0004-0.06). Prevotella abundance also correlated positively with scores of Fluid Cognition, Flanker Inhibitory Control and Attention, List Sorting, and Dimension Change Card Sort in MJ users, but not in non-users (interaction-p = 0.018-0.05). Similarly, mt function correlated positively with scores of Fluid Cognition and Flanker Inhibitory Control and Attention in MJ users, but not in non-users (interaction-p = 0.0018-0.08). These preliminary findings suggest that MJ use is associated with alterations of gut microbiota and mt function, which may further contribute to cognitive deficits. We posited that MJ-associated low vegetable/fruit intake may contribute to these changes. Future studies are needed to delineate the relationships among diet, microbiota, mt function, and cognition in MJ users.
MeSH term(s)	Adult ; Cognition/drug effects ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects ; Humans ; Leukocytes, Mononuclear/drug effects ; Male ; Marijuana Use/adverse effects ; Mitochondria/drug effects ; Pilot Projects ; Young Adult
Language	English
Publishing date	2017-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-017-9767-0
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Article ; Online: Subcutaneous Adipocyte Adenosine Triphosphate Levels in HIV Infected Patients.

Gojanovich, Greg S / Shikuma, Cecilia M / Milne, Cris / Libutti, Daniel E / Chow, Dominic C / Gerschenson, Mariana

AIDS research and human retroviruses

2019 Volume 36, Issue 1, Page(s) 75–82

Abstract: Lipoatrophy, or fat wasting, remains a syndrome plaguing ... ...

Abstract	Lipoatrophy, or fat wasting, remains a syndrome plaguing HIV
MeSH term(s)	Adenosine Triphosphate/analysis ; Adipocytes/metabolism ; Adult ; Aged ; Anti-HIV Agents/therapeutic use ; Cohort Studies ; Cross-Sectional Studies ; DNA, Mitochondrial/analysis ; Female ; HIV Infections/drug therapy ; HIV Infections/metabolism ; HIV-Associated Lipodystrophy Syndrome/metabolism ; Humans ; Male ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use ; Subcutaneous Fat/cytology
Chemical Substances	Anti-HIV Agents ; DNA, Mitochondrial ; Reverse Transcriptase Inhibitors ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2019-09-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/AID.2019.0121
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Article: Mitochondria and lipodystrophy: where are we now?

Gerschenson, Mariana

Antiviral therapy

2003 Volume 8, Issue 4, Page(s) 261–263

MeSH term(s)	Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Antiretroviral Therapy, Highly Active/adverse effects ; DNA, Mitochondrial/metabolism ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV-Associated Lipodystrophy Syndrome/pathology ; Humans ; Mitochondria/metabolism ; Mitochondria/pathology
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2003-08
Publishing country	England
Document type	Comment ; Editorial ; Review
ZDB-ID	1339842-8
ISSN	1359-6535
ISSN	1359-6535
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