Biology subjects

Neogi, U.

Publications and source records attributed to Neogi, U..

At least 19 recordsLinked to original sources

bioRxiv2026

The mitochondrial transaminase GOT2 supports Japanese encephalitis virus replication in neuronal cells

Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia, yet the host pathways that sustain its replication in the central nervous system remain poorly defined, and no antiviral therapies exist. Here we combine time-resolved transcriptomics and proteomics in mouse neuroblastoma (Neuro-2a) cells with time-resolved proteomics of infected mouse brain, integrated using directionality-penalized p-value merging. JEV infection was accompanied by progressive induction of interferon-stimulated proteins and by changes in the abundance of enzymes of central carbon and energy metabolism, spanning the tricarboxylic acid cycle, glycolysis, oxidative phosphorylation and glutaminolysis. Temporal clustering of the brain proteome linked oxidative phosphorylation remodelling to a dependence on glutamine metabolism. Glutamine antagonism with DON reduced viral RNA, whereas glycolytic inhibition and AKT modulation did not significantly alter it under the conditions tested. Silencing of the mitochondrial transaminase GOT2 reduced JEV RNA, viral protein, and infectious virus production in human SH-SY5Y cells. Our findings identify a glutamine-GOT2 axis as a metabolic dependency of JEV and a candidate host-directed antiviral target.

microbiology↗

bioRxiv2026

Integrated Clinical and Proteomic Precision Subgrouping for Severe Dengue Endotype Signature

BackgroundSevere dengue remains difficult to predict because patients with different clinical trajectories may present with overlapping features, and conventional severity classifications may not fully capture underlying biological heterogeneity. In this study, we applied an integrated clinical and proteomic endotyping approach to dissect dengue disease heterogeneity and identify molecular signatures associated with severity. MethodsPlasma proteomic profiles were analyzed together with detailed clinical, biochemical, hematological, coagulation, and immunological parameters from healthy controls and dengue patients classified according to WHO 2009 severity criteria. High-throughput proteomic analysis, unsupervised clustering, pathway enrichment, and machine-learning-based classification were used to identify dengue endotypes and define molecular features associated with predicted severe disease. ResultsIncreasing dengue severity was associated with progressive abnormalities in liver function, coagulation parameters, hematological indices, and inflammatory mediators, including IL-6, IL-15, HGF, and MUC-16. However, proteomic profiling revealed substantial overlap across conventional severity categories, indicating that clinical classification alone does not fully resolve dengue host-response heterogeneity. Integrated clinical-proteomic clustering identified distinct dengue endotypes, including a predicted severe endotype enriched for inflammatory, antiviral, and cytotoxic lymphocyte-associated pathways. This high-risk endotype was characterized by elevated IL-15, IFN-{gamma}, and granzymes, consistent with coordinated activation of cytotoxic lymphocyte-associated antiviral responses. Machine-learning analysis further showed that proteomic features were strong discriminators of this endotype, supporting their potential utility as biomarkers of severe host-response states. ConclusionIntegrated clinical-proteomic endotyping provides molecular resolution beyond conventional severity grading and identifies immune pathways associated with severe dengue. This framework may improve biological understanding of dengue progression and support future risk stratification and biomarker development.

systems biology↗

bioRxiv2026

ISG15-USP18 signaling restrains viperin-dependent metabolic antiviral restriction

Type I interferon (IFN-I) responses are tightly regulated to balance antiviral defense with cellular homeostasis. In humans, interferon-stimulated gene 15 (ISG15) functions as a critical negative regulator of IFN-I signaling by stabilizing the IFN negative regulator USP18, yet the functional consequences of ISG15 deficiency remain elusive. Here, we show that the loss of ISG15 exaggerates the JAK-STAT activation and, downstream, amplifies multiple ISGs including the nucleotide-modifying enzyme RSAD2 (viperin). Our quantitative proteomics, genetic reconstitution, and signaling analyses establish that defective USP18 stabilization skews the IFN response towards viperin expression. This amplified ISG network promotes viperin-catalyzed accumulation of the antiviral nucleotide analog ddhCTP, resulting in enhanced inhibition of viral RNA synthesis and the replication of Crimean-Congo hemorrhagic fever virus and SARS-CoV-2. Together, these findings demonstrate an ISG15-USP18-viperin axis that can be targeted to boost the metabolic antiviral restriction.

microbiology↗

bioRxiv2026

IFN-driven lipid synthesis shutdown in CD4⁺ T cells during acute SIV infection and persistent OXPHOS with ART initiation

Cellular metabolism regulates HIV/SIV replication and reservoir establishment, yet how infection and antiretroviral therapy initiation (ARTi) shape CD4 T cell metabolism in vivo remains poorly defined. Using the SIVmac239 macaque model, we integrated single-cell metabolic profiling (MIST), transcriptomics, lipidomics and genome-scale metabolic modeling to characterize their metabolic remodeling. At peak viremia, CD4 T cells exhibited shutdown of de novo fatty-acid (FA) synthesis, reflected by acetyl-CoA carboxylase-1 (ACC1) downregulation, inhibition of lipid-anabolic reactions, and depletion of membrane phospholipids. This state was driven by type I interferon (IFN-I) responses, and IFN-I suppressed ACC1 in vitro. Pharmacologic inhibition of FA synthesis enhanced T cell activation and exerted direct antiviral effects. Following ARTi, most metabolic pathways in CD4+ T cells were suppressed, whereas oxidative phosphorylation (OXPHOS) remained elevated and its levels in effector memory cells correlated with cell-associated-vDNA These findings identify IFN-driven FA synthesis suppression as a novel effector mechanism during acute viral infection, and persistent OXPHOS in effector CD4 T cells as a metabolic correlate of early reservoir establishment.

immunology↗

bioRxiv2025

Integrated Systems Vaccinology Reveals Distinct Metabolic Responses to SARS-CoV-2 Infection and DNA-Based Vaccines in Ferrets

Understanding systemic effects of vaccination and infection is central to defining correlates of protection against SARS-CoV-2. We used untargeted serum metabolomics to profile the immunometabolic landscape of ferrets after SARS-CoV-2 infection and DNA-/protein-based vaccination. Ferrets were vaccinated with either a multigenic DNA vaccine encoding SARS-CoV-2 RBD, M, and N (OC2), an N-only DNA vaccine (OC12), a recombinant spike protein with QS-21 adjuvant (S+QS21), or a hepatitis B/D control construct (Hep-B/D), and subsequently challenged with SARS-CoV-2. Serum was analyzed longitudinally at baseline, post-vaccination, and post-challenge. SARS-CoV-2 infection induced broad metabolic reprogramming, involving TCA cycle, glutathione metabolism, and nucleotide turnover, reflecting inflammation and cellular activation. OC2 vaccination induced strong metabolic shifts in amino acid and mitochondrial pathways despite low pre-challenge anti-S antibodies. Post-challenge, these shifts extended to redox and nucleotide pathways, correlating with robust anti-S and very strong anti-N antibody responses and complete viral clearance in BAL, but with marked airway pathology, consistent with T cell-mediated clearance of infected cells. S+QS21 and OC12 induced distinct, immunogen-specific signatures with partial protection, while Hep-B/D showed minimal systemic engagement. Metabolite-antibody correlations revealed vaccine-specific associations, highlighting lipid and amino acid pathways as potential immunogenicity biomarkers. Overlap and heatmap analyses showed that metabolic trajectories reflect both the magnitude and quality of immune training. These findings underscore the value of systems vaccinology in resolving mechanistic differences in vaccine responses and support metabolic profiling as a tool for evaluating immune efficacy in preclinical vaccine studies.

immunology↗

bioRxiv2025

Systemic Multi-Omics Analysis Reveals Interferon Response Heterogeneity and Links Lipid Metabolism to Immune Alterations in Severe COVID-19

The immune response to SARS-CoV-2 infection is highly heterogeneous, and interferon (IFN)-stimulated genes (ISGs) play a central but context-dependent role in antiviral defense and immune dysregulation. To investigate how ISG heterogeneity relates to immune and metabolic states, we performed an integrated analysis of whole-blood transcriptomics, plasma proteomics, metabolomics, and immune activation markers in hospitalized COVID-19 patients and COVID-negative healthy controls and covalescent individuals. Patients segregated into low (LIS), moderate (MIS), and high (HIS) ISG expression endotypes, largely independent of clinical severity. While high ISG expression was associated with systemic inflammation and innate immune activation, severe disease within the HIS endotype was characterized by marked metabolic perturbations, including depletion of tricarboxylic acid cycle intermediates and multiple lipid classes involved in membrane integrity and immunometabolic signaling. Plasma-transfer assays demonstrated that plasma from severe HIS patients impaired neutrophil and monocyte activation ex vivo, indicating functional attenuation of innate immune responses despite elevated ISG expression. These metabolic alterations correlated with reduced immune activation, supporting the existence of an interferon-associated immune-metabolic axis that constrains immune functionality in severe disease. Although type I IFN neutralization was detected in a subset of patients with IFN antigen reactivity, these samples did not account for ISG heterogeneity or disease severity. Together, these findings show that high ISG expression defines a transcriptional endotype permissive for inflammation but insufficient for effective immune function, highlighting the importance of immune-metabolic context in shaping COVID-19 disease outcomes.

immunology↗

bioRxiv2025

Disrupted α-ketoglutarate homeostasis trains monocyte-derived macrophages towards M2-like phenotype in long-term treated HIV-infection

Cells of the myeloid lineage, particularly monocytes and macrophages, are central to HIV pathogenesis, contributing to viral persistence and immune regulation during suppressive therapy. We hypothesized that metabolic reprogramming and altered chemokine signaling in people with HIV (PWH) on long-term ART impair monocyte trafficking and macrophage polarization. Using single-cell RNA sequencing, immunophenotyping, and metabolic modeling, we identified altered receptor expression and disrupted metabolic flux linked to reduced monocyte migration. Plasma secretome profiling revealed a nonclassical inflammatory microenvironment, while integrative multi-omics and single-cell proteomics of monocyte-derived macrophages (MDMs) demonstrated metabolic rewiring of the Glycolysis-TCA Anaplerosis Axis, orchestrated in part by elevated -ketoglutarate (AKG). Differentiation with PWH serum or AKG, skewed MDMs toward an M2-like phenotype, and enhanced HIV susceptibility. Together, these systems-level and mechanistic analyses reveal that metabolic training drives macrophage dysfunction in well-treated PWH, sustaining low-grade inflammation and highlighting potential therapeutic targets.

systems biology↗

bioRxiv2024

Parechovirus-3 infection disrupts immunometabolism and leads to glutamate excitotoxicity in neural organoids

Parechovirus ahumpari 3 (HPeV-3), is among the main agents causing severe neonatal neurological infections such as encephalitis and meningitis. However, the underlying molecular mechanisms and changes to the host cellular landscape leading to neurological disease has been understudied. Through quantitative proteomic analysis of HPeV-3 infected neural organoids, we identified unique metabolic changes following HPeV-3 infection that indicate immunometabolic dysregulation. Protein and pathway analyses showed significant alterations in neurotransmission and potentially, neuronal excitotoxicity. Elevated levels of extracellular glutamate, lactate dehydrogenase (LDH), and neurofilament light (NfL) confirmed glutamate excitotoxicity to be a key mechanism contributing to neuronal toxicity in HPeV-3 infection and can lead to apoptosis induced by caspase signaling. These insights are pivotal in delineating the metabolic landscape following severe HPeV-3 CNS infection and may identify potential host targets for therapeutic interventions.

neuroscience↗

bioRxiv2024

TISSUE-SPECIFIC METABOLOMIC REPROGRAMMING DETERMINES THE DISEASE PATHOPHYSIOLOGY OF SARS-COV-2 VARIANTS IN HAMSTER MODEL

Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between organs and specific SARS-CoV-2 variants, we sought to characterize the complex relationship among acute multisystem manifestations, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian Hamster (GSH) model using multi-omics approaches. Our investigation revealed increased viremia in diverse tissues of delta-infected GSH compared to the omicron variant. Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammation-associated taxa and reduced commensal bacteria compared to the omicron variant. These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection. TeaserIn hamsters at acute infection, SARS-CoV-2 variant-specific metabolic responses and gut dysbiosis dysregulate synaptic transmission proteins.

systems biology↗

bioRxiv2022

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

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PLWHART). 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 and metabolomic, and fecal 16s microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PLWHART. Through network analysis and similarity network fusion (SNF), we identified three groups of PLWHART (SNF-1 to 3). The PLWHART at SNF-2 (45%) was 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 healthy-like and severe at-risk group had a similar metabolic profile differing from HC, with dysregulation of amino acid metabolism. At the microbiome profile, the healthy-like group had a lower -diversity, a lower proportion of MSM, and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of men who have sex with men (MSM) confirming the influence of sexual orientation on the microbiome profile The multi-omics integrative analysis reveals a complex microbial interplay by microbiome-derived metabolites in PLWHART. PLWHART those are severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their metabolic profile. SignificanceThe network and factorization-based integrative analysis of plasma metabolomics, lipidomics, and microbiome profile identified three different diseases state -omics phenotypes within PLWHART driven by metabolomics, lipidomics, and microbiome that a single omics or clinical feature could not explain. The severe at-risk group has a dysregulated metabolic profile that potentiates metabolic diseases that could be barriers to healthy aging. The at-risk group may benefit from personalized medicine and lifestyle intervention to improve their metabolic profile.

bioinformatics↗

bioRxiv2021

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

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalised COVID-19 patients and compared those with the most severe outcome (i.e. death) to those with severe non-fatal disease, or mild/moderate disease, that recovered. A distinct subset of 8 cytokines and 140 metabolites in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the faecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts. In contrast, less severe clinical outcomes associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents.

immunology↗

bioRxiv2021

Deciphering the role of mucosal immune responses and cervicovaginal microbiome in resistance to HIV infection in HIV-exposed seronegative (HESN) women

The female genital tract (FGT) is an essential site of HIV infection. Discerning the nature of HIV-specific local immune responses is crucial for identifying correlates of protection in HIV-exposed seronegative (HESN) individuals. The present study involved a comprehensive analysis of soluble immune mediators, secretory immunoglobulins (sIg) and levels of natural killer (NK) cells, CXCR5+ CD8+T cells, T follicular helper cells (Tfh) and T regulatory cells (T regs) in the vaginal mucosa, as well as the nature and composition of the cervicovaginal microbiome in HESN women. We found significantly elevated antiviral cytokines, soluble immunoglobulins, and increased frequencies of activated NK cells, CXCR5+ CD8+ T cells and Tfh cells in HESN females as compared to HIV unexposed healthy (UH) women. Analysis of the genital microbiome of HESN women revealed a greater bacterial diversity and increased abundance of Gardnerella spp in the mucosa of HESN women. The findings suggest the female genital tract of HESN females represents a microenvironment equipped with innate immune factors, antiviral mediators and critical T cells subsets that protect against HIV infection.

immunology↗

bioRxiv2021

Cytotoxic lymphocytes target HIV-1 Gag through granzyme M-mediated cleavage

HIV-1 leads to progression to immunodeficiency and death of individuals who do not receive successful antiretroviral therapy. Initially, the hosts immune response controls the infection, but cannot eliminate the HIV-1 from the host. Cytotoxic lymphocytes are the key effector cells in this response and can mediate crucial antiviral responses through the release of a set of proteases called granzymes towards HIV-1-infected cells. However, little is known about the immunological molecular mechanisms by which granzymes could control HIV-1. Since we noted that HIV-1 subtype C (HIV-1C) Gag with the tetrapeptide insertion PYKE contains a putative granzyme M (GrM) cleavage site (KEPL) that overlaps with the PYKE insertion, we analyzed the proteolytic activity of GrM towards Gag. Immunoblot analysis showed that GrM could cleave Gag proteins from HIV-1B and variants from HIV-1C of which the Gag-PYKE variant was cleaved with extremely high efficiency. The main cleavage site was directly after the insertion after leucine residue 483. GrM-mediated cleavage of Gag was also observed in co-cultures using cytotoxic lymphocytes as effector cells and this cleavage could be inhibited by a GrM inhibitor peptide. Altogether, our data indicate towards a noncytotoxic immunological mechanism by which GrM-positive cytotoxic lymphocytes target the HIV-1 Gag protein within infected cells to potentially control HIV-1 infection. This mechanism could be exploited in new therapeutic strategies to treat HIV-1-infected patients to improve immunological control of the infection.

immunology↗

bioRxiv2021

Implications of central carbon metabolism in SARS-CoV-2 replication and disease severity

Viruses hijack host metabolic pathways for their replicative advantage. Several observational trans-omics analyses associated carbon and amino acid metabolism in coronavirus disease 2019 (COVID-19) severity in patients but lacked mechanistic insights. In this study, using patient- derived multi-omics data and in vitro infection assays, we aimed to understand i) role of key metabolic pathways in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reproduction and ii) its association with disease severity. Our data suggests that monocytes are key to the altered immune response during COVID-19. COVID-19 infection was associated with increased plasma glutamate levels, while glucose and mannose levels were determinants of the disease severity. Monocytes showed altered expression pattern of carbohydrate and amino acid transporters, GLUT1 and xCT respectively in severe COVID-19. Furthermore, lung epithelial cells (Calu-3) showed a strong acute metabolic adaptation following infection in vitro by modulating central carbon metabolism. We found that glycolysis and glutaminolysis are essential for virus replication and blocking these metabolic pathways caused significant reduction in virus production. Taken together, our study highlights that the virus utilizes and re-wires pathways governing central carbon metabolism leading to metabolic toxicity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity.

microbiology↗

bioRxiv2021

Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has caused a global health emergency. A key feature of COVID-19 is dysregulated interferon-response. Type-I interferon (IFN-I) is one of the earliest antiviral innate immune responses following viral infection and plays a significant role in the pathogenesis of SARS-CoV-2. In this study, using a proteomics-based approach, we identified that SARS-CoV-2 infection induces delayed and dysregulated IFN-I signaling in Huh7 cells. We demonstrate that SARS-CoV-2 is able to inhibit RIG-I mediated IFN-{beta} production. Our results also confirm the recent findings that IFN-I pretreatment is able to reduce susceptibility of Huh7 cells to SARS-CoV-2, but not post-treatment. Moreover, senescent Huh7 cells, in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection, and the virus effectively inhibited IFIT1 in these cells. Finally, proteomic comparison between SARS-CoV-2, SARS-CoV and MERS-CoV revealed a distinct differential regulatory signature of interferon-related proteins emphasizing that therapeutic strategies based on observations in SARS-CoV and MERS-CoV should be used with caution. Our findings provide a better understanding of SARS-CoV-2 regulation of cellular interferon response and a perspective on its use as a treatment. Investigation of different interferon stimulated genes and their role in inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.

microbiology↗

bioRxiv2020

Metabolic reprogramming and host-immune response against Crimean-Congo Hemorrhagic Fever Viruses

The pathogenesis and host-viral interactions of the Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and not well evaluated. Application of the multi-omics system biology approaches including biological network analysis in elucidating the complex host-viral response, allow for interrogating the viral pathogenesis. The present study aimed to fingerprint the system-level alterations during acute CCHFV-infection and the cellular immune responses during productive CCHFV-replication in vitro. We used system-wide network-based system biology analysis of peripheral blood mononuclear cells (PBMCs) from a longitudinal cohort of CCHF patients during the acute phase of infection and after one year of recovery (convalescent phase) and untargeted quantitative proteomics analysis of the most permissive CCHFV-infected Huh7 and SW13 cells. In the RNAseq analysis of the PBMCs, comparing the acute and convalescent-phase, we observed system-level hosts metabolic reprogramming towards central carbon and energy metabolism (CCEM) with distinct upregulation of oxidative phosphorylation (OXPHOS) during CCHFV-infection. Upon application of network-based system biology methods, negative coordination of the biological signaling systems like FOXO/Notch axis and Akt/mTOR/HIF-1 signaling with metabolic pathways during CCHFV-infection were observed. The temporal quantitative proteomics in Huh7 showed a dynamic change in the CCEM over time and was in agreement with the cross-sectional proteomics in SW13 cells. By blocking the two key CCEM pathways, glycolysis and glutaminolysis, viral replication was inhibited in vitro. Activation of key interferon stimulating genes during infection suggested the role of type I and II interferon-mediated antiviral mechanisms both at system-level and during progressive replication. Significance StatementA combination of multi-modal systems-wide host-immune response and in vitro temporal analysis identified molecular re-arrangement in CCEM and fingerprinting the interferon-mediated antiviral mechanism during CCHFV-infection. Using the newly gained insights, we then modulated the key pathways of CCEM by drugs and inhibited the productive CCHFV-replication in in vitro infection models. Our study thus provides a comprehensive, system-level picture of the regulation of cellular and metabolic pathways during productive CCHFV-infection for the first time that aids in identifying novel therapeutic targets and treatment strategies.

microbiology↗

bioRxiv2020

Replication dynamics and cytotoxicity of SARS-CoV-2 Swedish isolate in commonly used laboratory cell lines

The present pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is driving intense research activities to understand the basic biology of the virus and determine effective therapeutic strategies. The commonly used laboratory cell lines of human origin are the first line of experimental models to study the pathogenicity and performing antiviral assays. Thus, to find suitable cell models to study SARS-CoV-2, we assessed the tropism and cytopathogenicity of the first Swedish isolate of SARS-CoV-2 in six different cell lines of human origin and compared their growth characteristics to other globally isolated strains. Overall, Calu-3, Caco2, Huh7, and 293FT cell lines showed a high to moderate level of susceptibility to the majority of virus isolates. In Caco2 cells the virus can achieve high titers in the absence of any prominent cytopathic effect. The protein expression profile during SARS-CoV-2 infection revealed cell-type-specific regulation of cellular pathways. Type-I interferon signaling was identified as the common dysregulated cellular response in Caco2, Calu-3 and Huh7 cells. Overall, cell-type specific variability was noted for cytopathogenicity, susceptibility and cellular response to SARS-CoV-2. This study provides important clues regarding SARS-CoV-2 pathogenesis and can represent as a guide for future studies to design therapeutics.

microbiology↗

bioRxiv2020

Distinct lipid profile, low-level inflammation and increased antioxidant defense as a signature in HIV-1 elite control status

HIV-1 elite controllers (EC) are a rare but heterogeneous group of HIV-1-infected individuals who are able to suppress viral replication in the absence of antiretroviral therapy. The mechanisms of how EC achieve undetectable viral loads remain unclear. This study aimed to investigate host plasma metabolomics and targeted plasma proteomics in a Swedish HIV-1 cohort including EC and treatment-naive viremic progressors (VP) as well as HIV-negative individuals (HC) to get insights into mechanisms governing EC status. Metabolites belonging to antioxidant defense had higher levels in EC relative to VP while inflammation markers were increased in VP compared to EC. Only four plasma proteins (CCL4, CCL7, CCL20, and NOS3) were increased in EC compared to HC and CCL20/CCR6 axis can play important role. Our study suggests that low-level inflammation and oxidative stress at physiological levels could be important factors contributing to control of viral replication. One Sentence SummaryHIV-1 elite controllers had a distinct lipid profile, reduced inflammation, and increased antioxidant defense that might contribute to elite control status.

microbiology↗