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2. Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection

Author

Mikaeloff, Flora, Svensson Akusjärvi, Sara, Ikomey, George Mondinde, Krishnan, Shuba, Sperk, Maike, Gupta, Soham, Magdaleno, Gustavo Daniel Vega, Escós, Alejandra, Lyonga, Emilia, Okomo, Marie Claire, Tagne, Claude Tayou, Babu, Hemalatha, Lorson, Christian L., Végvári, Ákos, Banerjea, Akhil C., Kele, Julianna, Hanna, Luke Elizabeth, Singh, Kamal, de Magalhães, João Pedro, Benfeitas, Rui, and Neogi, Ujjwal

Published
2022
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8. Functional SARS-CoV-2 cross-reactive CD4 + T cells established in early childhood decline with age

Author

Humbert, Marion, primary, Olofsson, Anna, additional, Wullimann, David, additional, Niessl, Julia, additional, Hodcroft, Emma B., additional, Cai, Curtis, additional, Gao, Yu, additional, Sohlberg, Ebba, additional, Dyrdak, Robert, additional, Mikaeloff, Flora, additional, Neogi, Ujjwal, additional, Albert, Jan, additional, Malmberg, Karl-Johan, additional, Lund-Johansen, Fridtjof, additional, Aleman, Soo, additional, Björkhem-Bergman, Linda, additional, Jenmalm, Maria C., additional, Ljunggren, Hans-Gustaf, additional, Buggert, Marcus, additional, and Karlsson, Annika C., additional

Published
2023
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9. An integrative systems biology study to understand immune aging in people living with HIV

Author

Mikaeloff, Flora and Mikaeloff, Flora

Abstract

Antiretroviral therapy (ART) reduces viral replication, restores T helper cells and improves the survival of people living with HIV (PWH), transforming a life-threatening disease into a manageable chronic infection. Nevertheless, PWH under ART shows aging-related diseases such as bone abnormalities, non-HIV-associated cancers, and cardiovascular and neurocognitive diseases. The complex immune metabolic dysregulation leading to these comorbidities is called immune aging. The main question raised by my thesis was, what are the complex mechanisms responsible for immune aging in HIV? Using advanced system biology and machine learning tools, I used multi-omics-based patient stratification to identify biologic perturbations associated with immune aging in PWH. First, we investigated PWH with Metabolic Syndrome (MetS), a relatively common agingrelated disease in HIV-1. In paper I, we identified the dysregulation of glutamate metabolism in PWH with MetS using plasma metabolomics and measure of cell transporters by flow cytrometry. Then, we investigated the mechanisms of differing PWH on long-term successful ART from HIV-negative controls (HC). In paper II, we identified the dysregulation of amino acids and, more specifically, glutaminolysis (i.e., lysis of glutamine to glutamate) in PWH compared to HC using metabolomics in two independent cohorts to avoid the potential cohort biases. We identified five neurosteroids to be lower in PWH and potentially create neurological impairments in PWH. The glutaminolysis inhibition in chronically infected HIV-1 promonocytic (U1) cells induced apoptosis and latency reversal which could clear HIV reservoirs. The first two papers universally clarified our knowledge about dysregulated metabolic traits following a prolonged ART in PWH. However, we observed heterogeneity among the clinically defined PWH. Therefore, we focused more on the multi-omics data-driven approaches to stratify the at-risk group who were either dysregulated metabolicall

Published
2023

10. Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

Author

Mikaeloff, Flora, Gelpi, Marco, Benfeitas, Rui, Knudsen, Andreas D., Vestad, Beate, Hogh, Julie, Hov, Johannes R., Benfield, Thomas, Murray, Daniel, Giske, Christian G., Mardinoglu, Adil, Troseid, Marius, Nielsen, Susanne D., Neogi, Ujjwal, Hens, Niel, Mikaeloff, Flora, Gelpi, Marco, Benfeitas, Rui, Knudsen, Andreas D., Vestad, Beate, Hogh, Julie, Hov, Johannes R., Benfield, Thomas, Murray, Daniel, Giske, Christian G., Mardinoglu, Adil, Troseid, Marius, Nielsen, Susanne D., Neogi, Ujjwal, and Hens, Niel

Abstract

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1-3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4(+) T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower alpha-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging., QC 20230414

Published
2023
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11. Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

Author

Mikaeloff, Flora, primary, Gelpi, Marco, additional, Benfeitas, Rui, additional, Knudsen, Andreas D, additional, Vestad, Beate, additional, Høgh, Julie, additional, Hov, Johannes R, additional, Benfield, Thomas, additional, Murray, Daniel, additional, Giske, Christian G, additional, Mardinoglu, Adil, additional, Trøseid, Marius, additional, Nielsen, Susanne D, additional, and Neogi, Ujjwal, additional

Published
2023
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12. Author response: Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

Author

Mikaeloff, Flora, primary, Gelpi, Marco, additional, Benfeitas, Rui, additional, Knudsen, Andreas D, additional, Vestad, Beate, additional, Høgh, Julie, additional, Hov, Johannes R, additional, Benfield, Thomas, additional, Murray, Daniel, additional, Giske, Christian G, additional, Mardinoglu, Adil, additional, Trøseid, Marius, additional, Nielsen, Susanne D, additional, and Neogi, Ujjwal, additional

Published
2023
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13. Impaired Immuno-Metabolic Homeostasis and Microenvironmental Influence on Neuropsychiatric Risk in Treated HIV Infection

Author

Mikaeloff, Flora, primary, Gelpi, Marco, additional, Escós, Alejandra, additional, Wang, Tianqi, additional, Olofsson, Anna, additional, Svensson-Akusjärvi, Sara, additional, Schuster, Sabrina, additional, Naval, Prajakta, additional, Sood, Vikas, additional, Nikouyan, Negin, additional, Knudsen, Andreas, additional, Vestad, Beate, additional, Høgh, Julie, additional, Hov, Johannes Roksund, additional, Benfield, Thomas, additional, Trøseid, Marius, additional, Gupta, Soham, additional, Pawar, Vinay, additional, Rucevic, Marijana, additional, Benfeitas, Rui, additional, Végvári, Ákos, additional, O’Mahony, Liam, additional, Savai, Rajkumar, additional, Bjorkstrom, Niklas, additional, Lourda, Magda, additional, de Magalhães, João Pedro, additional, Weiss, Siegfried, additional, Mardinoglu, Adil, additional, Karlsson, Annika, additional, Syed, Yasir Ahmed, additional, Nielsen, Susanne Dam, additional, and Neogi, Ujjwal, additional

Published
2023
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14. The central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome

Author

Gelpi, Marco, Mikaeloff, Flora, Knudsen, Andreas D., Benfeitas, Rui, Krishnan, Shuba, Akusjärvi, Sara Svenssson, Høgh, Julie, Murray, Daniel D., Ullum, Henrik, Neogi, Ujjwal, and Nielsen, Susanne D.

Subjects
Male, Metabolic Syndrome, Anti-HIV Agents, antiretroviral therapy, Glutamic Acid, HIV Infections, Middle Aged, immune-phenotyping, metabolomics, metabolic syndrome, Carbohydrate Metabolism, Humans, Female, Amino Acids, HIV-infection, Research Paper
Abstract

Metabolic syndrome (MetS) is a significant factor for cardiometabolic comorbidities in people living with HIV (PLWH) and a barrier to healthy aging. The long-term consequences of HIV-infection and combination antiretroviral therapy (cART) in metabolic reprogramming are unknown. In this study, we investigated metabolic alterations in well-treated PLWH with MetS to identify potential mechanisms behind the MetS phenotype using advanced statistical and machine learning algorithms. We included 200 PLWH from the Copenhagen Comorbidity in HIV-infection (COCOMO) study. PLWH were grouped into PLWH with MetS (n= 100) defined according to the International Diabetes Federation (IDF) consensus worldwide definition of the MetS or without MetS (n= 100). The untargeted plasma metabolomics was performed using ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS/MS) and immune-phenotyping of Glut1 (glucose transporter), xCT (glutamate/cysteine transporter) and MCT1 (pyruvate/lactate transporter) by flow cytometry. We applied several conventional approaches, machine learning algorithms, and linear classification models to identify the biologically relevant metabolites associated with MetS in PLWH. Of the 877 identified biochemicals, 9% (76/877) differed significantly between PLWH with and without MetS (false discovery rate

Published
2021

15. Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection

Author

Mikaeloff, Flora, primary, Gelpi, Marco, additional, Benfeitas, Rui, additional, Knudsen, Andreas D., additional, Vestad, Beate, additional, Høgh, Julie, additional, Hov, Johannes R., additional, Benfield, Thomas, additional, Murray, Daniel, additional, Giske, Christian G, additional, Mardinoglu, Adil, additional, Trøseid, Marius, additional, Nielsen, Susanne D., additional, and Neogi, Ujjwal, additional

Published
2022
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16. A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2

Author

Albrich, Werner C., primary, Ghosh, Tarini Shankar, additional, Ahearn-Ford, Sinead, additional, Mikaeloff, Flora, additional, Lunjani, Nonhlanhla, additional, Forde, Brian, additional, Suh, Noémie, additional, Kleger, Gian-Reto, additional, Pietsch, Urs, additional, Frischknecht, Manuel, additional, Garzoni, Christian, additional, Forlenza, Rossella, additional, Horgan, Mary, additional, Sadlier, Corinna, additional, Negro, Tommaso Rochat, additional, Pugin, Jérôme, additional, Wozniak, Hannah, additional, Cerny, Andreas, additional, Neogi, Ujjwal, additional, O’Toole, Paul W., additional, and O’Mahony, Liam, additional

Published
2022
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18. Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

Author

Appelberg, Sofia, Gupta, Soham, Svensson Akusjärvi, Sara, Ambikan, Anoop T., Mikaeloff, Flora, Saccon, Elisa, Végvári, Ákos, Benfeitas, Rui, Sperk, Maike, Ståhlberg, Marie, Krishnan, Shuba, Singh, Kamal, Penninger, Josef M., Mirazimi, Ali, and Neogi, Ujjwal

Subjects
Proteomics, Epidemiology, viruses, Immunology, Pneumonia, Viral, Microbiology, Cell Line, transcriptomics, Akt/mTOR/HIF-1, Betacoronavirus, Tandem Mass Spectrometry, Virology, Drug Discovery, Humans, Pandemics, SARS-CoV-2, Gene Expression Profiling, TOR Serine-Threonine Kinases, COVID-19, High-Throughput Nucleotide Sequencing, General Medicine, Articles, Infectious Diseases, MK-2206, Gene Expression Regulation, Parasitology, Hypoxia-Inducible Factor 1, Coronavirus Infections, Proto-Oncogene Proteins c-akt, Research Article, Chromatography, Liquid, Signal Transduction
Abstract

How severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remains largely elusive. We performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected Huh7 cells to map the cellular response to the invading virus over time. We identified four pathways, ErbB, HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector molecules of these pathways revealed a dose-dependent activation of Akt, mTOR, S6K1 and 4E-BP1 at 24 hours post infection (hpi). However, we found a significant inhibition of HIF-1α through 24hpi and 48hpi of the infection, suggesting a crosstalk between the SARS-CoV-2 and the Akt/mTOR/HIF-1 signaling pathways. Inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206 showed a significant reduction in virus production. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe coronavirus disease 2019 (COVID-19) patients.

Published
2020

19. Nucleoside-Modified mRNA Vaccines Protect IFNAR –/– Mice against Crimean-Congo Hemorrhagic Fever Virus Infection

Author

Appelberg, Sofia, primary, John, Lijo, additional, Pardi, Norbert, additional, Végvári, Ákos, additional, Bereczky, Sándor, additional, Ahlén, Gustaf, additional, Monteil, Vanessa, additional, Abdurahman, Samir, additional, Mikaeloff, Flora, additional, Beattie, Mitchell, additional, Tam, Ying, additional, Sällberg, Matti, additional, Neogi, Ujjwal, additional, Weissman, Drew, additional, and Mirazimi, Ali, additional

Published
2022
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20. Integrative proteo-transcriptomic and immunophenotyping signatures of HIV-1 elite control phenotype: A cross-talk between glycolysis and HIF signaling

Author

Akusjärvi, Sara Svensson, primary, Ambikan, Anoop T., additional, Krishnan, Shuba, additional, Gupta, Soham, additional, Sperk, Maike, additional, Végvári, Ákos, additional, Mikaeloff, Flora, additional, Healy, Katie, additional, Vesterbacka, Jan, additional, Nowak, Piotr, additional, Sönnerborg, Anders, additional, and Neogi, Ujjwal, additional

Published
2022
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21. Distinct Metabolic Profile Associated with a Fatal Outcome in COVID-19 Patients during the Early Epidemic in Italy

Author

Saccon, Elisa, Bandera, Alessandra, Sciumè, Mariarita, Mikaeloff, Flora, Lashari, Abid A., Aliberti, Stefano, Sachs, Michael C., Billi, Filippo, Blasi, Francesco, Gabriel, Erin E., Costantino, Giorgio, De Roberto, Pasquale, Krishnan, Shuba, Gori, Andrea, Peyvandi, Flora, Scudeller, Luigia, Canetta, Ciro, Lorson, Christian L., Valenti, Luca, Singh, Kamal, Baldini, Luca, Fracchiolla, Nicola Stefano, and Neogi, Ujjwal

Subjects
Aged, 80 and over, Male, SARS-CoV-2, fatal outcome, COVID-19, Observation, Comorbidity, Middle Aged, Prognosis, metabolomics, Microbiology, QR1-502, predictive biomarkers, Italy, Metabolome, Humans, Female, Energy Metabolism, Biomarkers, Blood Chemical Analysis, Aged, Retrospective Studies
Abstract

In one year of the coronavirus disease 2019 (COVID-19) pandemic, many studies have described the different metabolic changes occurring in COVID-19 patients, linking these alterations to the disease severity. However, a complete metabolic signature of the most severe cases, especially those with a fatal outcome, is still missing. Our study retrospectively analyzes the metabolome profiles of 75 COVID-19 patients with moderate and severe symptoms admitted to Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (Lombardy Region, Italy) following SARS-CoV-2 infection between March and April 2020. Italy was the first Western country to experience COVID-19, and the Lombardy Region was the epicenter of the Italian COVID-19 pandemic. This cohort shows a higher mortality rate compared to others; therefore, it represents a unique opportunity to investigate the underlying metabolic profiles of the first COVID-19 patients in Italy and to identify the potential biomarkers related to the disease prognosis and fatal outcome. IMPORTANCE Understanding the metabolic alterations occurring during an infection is a key element for identifying potential indicators of the disease prognosis, which are fundamental for developing efficient diagnostic tools and offering the best therapeutic treatment to the patient. Here, exploiting high-throughput metabolomics data, we identified the first metabolic profile associated with a fatal outcome, not correlated with preexisting clinical conditions or the oxygen demand at the moment of diagnosis. Overall, our results contribute to a better understanding of COVID-19-related metabolic disruption and may represent a useful starting point for the identification of independent prognostic factors to be employed in therapeutic practice.

Published
2021

22. Excessive inflammatory and metabolic responses to acute SARS-CoV-2 infection are associated with a distinct gut microbiota composition

Author

Albrich, Werner C., primary, Ghosh, Tarini Shankar, additional, Ahearn-Ford, Sinead, additional, Mikaeloff, Flora, additional, Lunjani, Nonhlanhla, additional, Forde, Brian, additional, Suh, Noémie, additional, Kleger, Gian-Reto, additional, Pietsch, Urs, additional, Frischknecht, Manuel, additional, Garzoni, Christian, additional, Forlenza, Rossella, additional, Horgan, Mary, additional, Sadlier, Corinna, additional, Negro, Tommaso Rochat, additional, Pugin, Jérôme, additional, Wozniak, Hannah, additional, Cerny, Andreas, additional, Neogi, Ujjwal, additional, O’Toole, Paul W., additional, and O’Mahony, Liam, additional

Published
2021
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23. Fecal Metabolome Signature in the HIV-1 Elite Control Phenotype: Enrichment of Dipeptides Acts as an HIV-1 Antagonist but a Prevotella Agonist

Author

Sperk, Maike, primary, Ambikan, Anoop T., additional, Ray, Shilpa, additional, Singh, Kamal, additional, Mikaeloff, Flora, additional, Diez, Rafael Ceña, additional, Narayanan, Ashwathy, additional, Vesterbacka, Jan, additional, Nowak, Piotr, additional, Sönnerborg, Anders, additional, and Neogi, Ujjwal, additional

Published
2021
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24. Trans Cohorts Metabolomic Modulation Following Long-Term Successful Therapy in HIV-Infection

Author

Mikaeloff, Flora, primary, Svensson-Akusjärvi, Sara, additional, Ikomey, George Mondinde, additional, Krishnan, Shuba, additional, Sperk, Maike, additional, Gupta, Soham, additional, Vega Magdaleno, Gustavo Daniel, additional, Escós, Alejandra, additional, Lyonga, Emilia, additional, Okomo, Marie Claire, additional, Tagne, Claude Tayou, additional, Babu, Hemalatha, additional, Lorson, Christian L, additional, Végvári, Ákos, additional, Banerjea, Akhil C., additional, Kele, Julianna, additional, Hanna, Luke Elizabeth, additional, Singh, Kamal, additional, de Magalhães, João Pedro, additional, Benfeitas, Rui, additional, and Neogi, Ujjwal, additional

Published
2021
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26. Metabolic perturbation associated with COVID-19 disease severity and SARS-CoV-2 replication

Author

Krishnan, Shuba, Nordqvist, Hampus, Ambikan, Anoop T., Gupta, Soham, Sperk, Maike, Svensson-Akusjärvi, Sara, Mikaeloff, Flora, Benfeitas, Rui, Saccon, Elisa, Ponnan, Sivasankaran Munusamy, Rodriguez, Jimmy Esneider, Nikouyan, Negin, Odeh, Amani, Ahlén, Gustaf, Asghar, Muhammad, Sällberg, Matti, Vesterbacka, Jan, Nowak, Piotr, Végvári, Ákos, Sönnerborg, Anders, Treutiger, Carl Johan, and Neogi, Ujjwal

Subjects
Adult, Glucose Transporter Type 1, Infectious Medicine, Amino Acid Transport System y+, SARS-CoV-2, Research, Carbohydrates, Biochemistry and Molecular Biology, COVID-19, Infektionsmedicin, Blood Proteins, Middle Aged, Virus Replication, Mannose-Binding Lectin, Severity of Illness Index, Immunophenotyping, Hospitalization, Case-Control Studies, Humans, Amino Acids, Mannose, Biomarkers, Biokemi och molekylärbiologi, Aged
Abstract

Viruses hijack host metabolic pathways for their replicative advantage. In this study, using patient-derived multi-omics data and in vitro infection assays, we aimed to understand the role of key metabolic pathways that can regulate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reproduction and their association with disease severity. We used multi-omics platforms (targeted and untargeted proteomics and untargeted metabolomics) on patient samples and cell line models along with immune phenotyping of metabolite transporters in patient blood to understand viral-induced metabolic modulations. We also modulated key metabolic pathways that were identified using multi-omics data to regulate the viral reproduction in vitro. COVID-19 disease severity was characterized by increased plasma glucose and mannose levels. Immune phenotyping identified altered expression patterns of carbohydrate transporter, GLUT1, in CD8+ T-cells, intermediate and non-classical monocytes, and amino acid transporter, xCT, in classical, intermediate, and non-classical monocytes. In in vitro lung epithelial cell (Calu-3) infection model we found that glycolysis and glutaminolysis are essential for virus replication and blocking these metabolic pathways caused significant reduction in virus production. Taken together, we therefore hypothesized that SARS-CoV-2 utilizes and rewires pathways governing central carbon metabolism leading to the efflux of toxic metabolites and associated with disease severity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity., Graphical abstract

Published
2021

28. Central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome: a cross-sectional cohort study

Author

Gelpi, Marco, primary, Mikaeloff, Flora, additional, Dehlbæk Knudsen, Andreas, additional, Benfeitas, Rui, additional, Krishnan, Shuba, additional, Høgh, Julie, additional, Murray, Daniel D., additional, Ullum, Henrik, additional, Neogi, Ujjwal, additional, and Dam Nielsen, Susanne, additional

Published
2021
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29. Implications of central carbon metabolism in SARS-CoV-2 replication and disease severity

Author

Krishnan, Shuba, primary, Nordqvist, Hampus, additional, Ambikan, Anoop T., additional, Gupta, Soham, additional, Sperk, Maike, additional, Svensson-Akusjärvi, Sara, additional, Mikaeloff, Flora, additional, Benfeitas, Rui, additional, Saccon, Elisa, additional, Ponnan, Sivasankaran Munusamy, additional, Rodriguez, Jimmy Esneider, additional, Nikouyan, Negin, additional, Odeh, Amani, additional, Ahlén, Gustaf, additional, Asghar, Muhammad, additional, Sällberg, Matti, additional, Vesterbacka, Jan, additional, Nowak, Piotr, additional, Végvári, Ákos, additional, Sönnerborg, Anders, additional, Treutiger, Carl Johan, additional, and Neogi, Ujjwal, additional

Published
2021
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30. Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells

Author

Chen, Xi, primary, Saccon, Elisa, additional, Appelberg, K. Sofia, additional, Mikaeloff, Flora, additional, Rodriguez, Jimmy Esneider, additional, Vinhas, Beatriz Sá, additional, Frisan, Teresa, additional, Végvári, Ákos, additional, Mirazimi, Ali, additional, Neogi, Ujjwal, additional, and Gupta, Soham, additional

Published
2021
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31. Metabolic Perturbation Associated With COVID-19 Disease Severity and SARS-CoV-2 Replication

Author

Krishnan, Shuba, primary, Nordqvist, Hampus, additional, Ambikan, Anoop T., additional, Gupta, Soham, additional, Sperk, Maike, additional, Svensson-Akusjärvi, Sara, additional, Mikaeloff, Flora, additional, Benfeitas, Rui, additional, Saccon, Elisa, additional, Ponnan, Sivasankaran Munusamy, additional, Rodriguez, Jimmy Esneider, additional, Nikouyan, Negin, additional, Odeh, Amani, additional, Ahlén, Gustaf, additional, Asghar, Muhammad, additional, Sällberg, Matti, additional, Vesterbacka, Jan, additional, Nowak, Piotr, additional, Végvári, Ákos, additional, Sönnerborg, Anders, additional, Treutiger, Carl Johan, additional, and Neogi, Ujjwal, additional

Published
2021
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32. Integrative Proteo-Transcriptomic and Immunophenotyping Signatures of HIV-1 Elite Control Phenotype: A Cross-Talk Between Glycolysis and HIF Signaling

Author

Svensson-Akusjärvi, Sara, primary, Ambikan, Anoop T., additional, Krishnan, Shuba, additional, Gupta, Soham, additional, Sperk, Maike, additional, Végvári, Ákos, additional, Mikaeloff, Flora, additional, Healy, Katie, additional, Vesterbacka, Jan, additional, Nowak, Piotr, additional, Sönnerborg, Anders, additional, and Neogi, Ujjwal, additional

Published
2021
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35. Tropism of SARS-CoV-2 in commonly used laboratory cell lines and their proteomic landscape during infection

Author

Saccon, Elisa, primary, Chen, Xi, additional, Mikaeloff, Flora, additional, Rodriguez, Jimmy Esneider, additional, Szekely, Laszlo, additional, Sá Vinhas, Beatriz, additional, Krishnan, Shuba, additional, Byrareddy, Siddappa N., additional, Frisan, Teresa, additional, Végvári, Ákos, additional, Mirazimi, Ali, additional, Neogi, Ujjwal, additional, and Gupta, Soham, additional

Published
2020
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37. Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

Author

Appelberg, Sofia, primary, Gupta, Soham, additional, Ambikan, Anoop T, additional, Mikaeloff, Flora, additional, Végvári, Ákos, additional, Akusjärvi, Sara Svensson, additional, Benfeitas, Rui, additional, Sperk, Maike, additional, Ståhlberg, Marie, additional, Krishnan, Shuba, additional, Singh, Kamal, additional, Penninger, Josef M., additional, Mirazimi, Ali, additional, and Neogi, Ujjwal, additional

Published
2020
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39. Integrative proteo-transcriptomic and immunophenotyping signatures of HIV-1 elite control phenotype: A cross-talk between glycolysis and HIF signaling.

Author

Akusjärvi SS, Ambikan AT, Krishnan S, Gupta S, Sperk M, Végvári Á, Mikaeloff F, Healy K, Vesterbacka J, Nowak P, Sönnerborg A, and Neogi U

Abstract

Natural control of HIV-1 is a characteristic of <1% of HIV-1-infected individuals, so called elite controllers (EC). In this study, we sought to identify signaling pathways associated with the EC phenotype using integrative proteo-transcriptomic analysis and immunophenotyping. We found HIF signaling and glycolysis as specific traits of the EC phenotype together with dysregulation of HIF target gene transcription. A higher proportion of HIF-1α and HIF-1β in the nuclei of CD4 + and CD8 + T cells in the male EC were observed, indicating a potential increased activation of the HIF signaling pathway. Furthermore, intracellular glucose levels were elevated in EC even as the surface expression of the metabolite transporters Glut1 and MCT-1 were decreased on lymphocytes indicative of unique metabolic uptake and flux profile. Combined, our data show that glycolytic modulation and altered HIF signaling is a unique feature of the male EC phenotype that may contribute to natural control of HIV-1., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Published
2021
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