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Prasad, P.

Publications and source records attributed to Prasad, P..

35 records · Page 2Linked to original sources
bioRxiv2023

Improved bladder cancer antitumor efficacy with a recombinant BCG that releases a STING agonist

Despite the introduction of several new agents for the treatment of bladder cancer (BC), intravesical BCG remains a first line agent for the management of non-muscle invasive bladder cancer. In this study we evaluated the antitumor efficacy in animal models of BC of a recombinant BCG known as BCG-disA-OE that releases the small molecule STING agonist c-di-AMP. We found that compared to wild-type BCG (BCG-WT), in both the orthotopic, carcinogen-induced rat MNU model and the heterotopic syngeneic mouse MB-49 model BCG-disA-OE afforded improved antitumor efficacy. A mouse safety evaluation further revealed that BCG-disA-OE proliferated to lesser degree than BCG-WT in BALB/c mice and displayed reduced lethality in SCID mice. To probe the mechanisms that may underlie these effects, we found that BCG-disA-OE was more potent than BCG-WT in eliciting IFN-{beta} release by exposed macrophages, in reprogramming myeloid cell subsets towards an M1-like proinflammatory phenotypes, inducing epigenetic activation marks in proinflammatory cytokine promoters, and in shifting monocyte metabolomic profiles towards glycolysis. Many of the parameters elevated in cells exposed to BCG-disA-OE are associated with BCG-mediated trained innate immunity suggesting that STING agonist overexpression may enhance trained immunity. These results indicate that modifying BCG to release high levels of proinflammatory PAMP molecules such as the STING agonist c-di-AMP can enhance antitumor efficacy in bladder cancer.

cancer biology↗
bioRxiv2023

Human Heart Failure Alters Mitochondria and Fiber 3D Structure Triggering Metabolic Shifts

This study, utilizing SBF-SEM, reveals structural alterations in mitochondria and myofibrils in human heart failure (HF). Mitochondria in HF show changes in structure, while myofibrils exhibit increased cross-sectional area and branching. Metabolomic and lipidomic analyses indicate concomitant dysregulation in key pathways. The findings underscore the need for personalized treatments considering individualized structural changes in HF.

physiology↗
bioRxiv2023

Metallo-protease Peptidase M84 from Bacillus altitudinis induces ROS dependent apoptosis in ovarian cancer cells by targeting PAR-1

In pursuit of isolating novel anticancer proteases from environmental microbial isolates, we have purified and identified an extracellular metallo-protease from Bacillus altitudinis named Peptidase M84. This protease selectively triggered apoptosis in human ovarian adenocarcinoma cells (PA-1, SKOV3) and mouse ovarian carcinoma cells (ID8), in addition to exhibiting no significant effect on normal human epithelial ovarian cell (IOSE) and mouse peritoneal macrophage (PEM[FE]) cell viabilities. Protease activated receptor-1 (PAR-1); a GPCR which is reported to be overexpressed in ovarian cancer cells was identified as a novel target of Peptidase M84. We observed that Peptidase M84 induced PAR-1 overexpression along with activating its downstream signalling effectors NF{kappa}B and MAPK to promote excessive reactive oxygen species (ROS) generation in ovarian cancer cells. This disrupted mitochondrial membrane potential, allowed cytosolic release of mitochondrial cytochrome c, increased the Bax (pro-apoptotic) to Bcl-2 (anti-apoptotic) ratio and promoted DNA damage to evoke apoptotic death of the ovarian cancer cells. Peptidase M84 also reduced nuclear ki-67 expression in these malignant cells to render an anti-proliferative role. In in vivo set-up, weekly intraperitoneal administration of Peptidase M84 (12 {micro}g/kg body-weight) in the ID8 mice model significantly diminished ascitic fluid accumulation through induction of oxidative stress, increasing murine survival rates by 60%. Collectively, our in vitro and in vivo findings suggested that Peptidase M84 triggered PAR-1 mediated oxidative stress to act as an apoptosis inducer in ovarian cancer cells. This established Peptidase M84 as a promising drug candidate for receptor mediated targeted-therapy of ovarian cancer. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=158 HEIGHT=200 SRC="FIGDIR/small/556500v2_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@6b0a19org.highwire.dtl.DTLVardef@1640510org.highwire.dtl.DTLVardef@1888b49org.highwire.dtl.DTLVardef@1708114_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗
bioRxiv2023

Huntingtin Interacting Protein-1 expression is regulated via HIF2 axis in Lung Adenocarcinoma

Non-Small Cell Lung Cancer (NSCLC) patients are diagnosed late when the disease has metastasized. Kras is a prevalent mutation in NSCLC besides EGFR and TP53 and targeted therapies against this have been challenging. We have explored deregulation of an endocytic adapter protein, Huntingtin Interacting Protein-1(HIP1) and its relevance in a Kras mutant lung adenocarcinoma cell line as a model system. HIP1 RNA expression is observed to be significantly reduced in high-grade and metastatic lung cancer patients as compared to low-grade tumours and this correlates with poor survival. HIP1 depletion followed by global proteome profiling in A549 cells identified metabolic pathways to be majorly upregulated, followed by RNA transport and surveillance, amongst others. HIP1 depletion also significantly increased anchorage independent growth and invasion of these cells. However, the EMT markers did not follow the canonical regulation. We observed E-Cadherin and Vimentin induction, which is suggestive of collective migration. Additionally, we observed a hypoxic microenvironment to induce HIP1 expression, mediated by Hypoxia Inducible Factor 2 (HIF2), suggesting that a HIF2-HIP1 axis can cause tumour suppression and needs further exploration.

cancer biology↗
bioRxiv2022

Transgenic Mouse Models Establish a Protective Role of Type 1 IFN Response in SARS-CoV-2 infection-related Immunopathology

Type 1 interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infections remained to be perplexing. Here, we developed two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1-/-) and the other with dampened IFN-I response (hACE2; Ifnar1-/-) to comprehend the role of IFN-I response during SARS-CoV-2 invasion. We found that hACE2; Irgm1-/- mice were resistant to lethal SARS-CoV-2 infection with substantially reduced cytokine storm and immunopathology. In striking contrast, a severe SARS-CoV-2 infection along with immune cells infiltration, inflammatory response, and enhanced pathology was observed in the lungs of hACE2; Ifnar1-/- mice. Additionally, hACE2; Ifnar1-/- mice were highly susceptible to SARS-CoV-2 neuroinvasion in the brain accompanied by immune cell infiltration, microglia/astrocytes activation, cytokine response, and demyelination of neurons. The hACE2; Irgm1-/- Ifnar1-/- double knockout mice or hACE2; Irgm1-/- mice treated with STING or RIPK2 pharmacological inhibitors displayed loss of the protective phenotypes observed in hACE2; Irgm1-/- mice suggesting that heightened IFN-I response accounts for the observed immunity. Taken together, we explicitly demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/520843v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@a3aad4org.highwire.dtl.DTLVardef@12452fcorg.highwire.dtl.DTLVardef@1c43dc0org.highwire.dtl.DTLVardef@b2167d_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗
bioRxiv2022

Adjunctive inhibition of the integrated stress response pathway accelerates bacterial clearance in a mouse model of tuberculosis

Tuberculosis (TB) is a devastating infectious disease that continues to cause millions of human deaths every year. Even though most cases of TB can be cured with a 6-month antibiotic combination therapy, these long treatment durations have led to the emergence of multi-drug resistance and pose a major hurdle to global TB control. Despite numerous advances in TB drug development, a substantially shortened treatment time has yet to be achieved. Given the rise in antibiotic resistance, an alternative strategy to the direct targeting of M. tuberculosis (M.tb) is the development of host-directed therapies (HDTs) that promote bacterial clearance and/or lung health when given adjunctive to standard TB antibiotics. We recently discovered that a small molecule inhibitor of the Integrated Stress Response (ISR), which is abnormally activated in TB and associated with the formation of necrotic granulomas, reduced M.tb numbers and lung inflammation in mice. Here, we evaluated the therapeutic potential of adjunctive ISR inhibition in the context of standard TB therapy. Throughout the course of treatment, ISR inhibition robustly lowered bacterial burdens compared to standard TB therapy alone and accelerated the time-to-sterility in mice, as demonstrated by significantly reduced relapse rates after 4 months of treatment. In addition, mice receiving adjunctive ISR inhibition tended to have reduced lung necrosis and inflammation. Together, our findings identify the ISR pathway as a promising therapeutic target with the potential of shortening TB treatment durations and improving lung health.

microbiology↗
bioRxiv2021

Isolation and Characterization of SARS-CoV-2 strains circulating in Eastern India.

Emergence of SARS-CoV-2 as a serious pandemic has altered the global socioeconomic dynamics. The wide prevalence, high death counts and rapid emergence of new variants urge for establishment of research infrastructure to facilitate rapid development of efficient therapeutic modalities and preventive measures. In agreement with this, five SARS-CoV2 strains (ILS01, ILS02, ILS03, ILS15 and ILS24) of four different clades (19A, 19B, 20A and 20B) were isolated from patient swab samples collected during the 1st COVID-19 wave in Odisha, India. The viral isolates were adapted to in-vitro cultures and further characterized to identify strain specific variations in viral growth characteristics. All the five isolates showed substantial amount of virus induced CPE however ILS03 belonging to 20A clade displayed highest level of CPE. Time kinetics experiment revealed spike protein expression was evident after 16th hours post infection in all five isolates. ILS03 induced around 90% of cytotoxicity. Further, the susceptibility of various cell lines (human hepatoma cell line (Huh-7), CaCo2 cell line, HEK-293T cells, Vero, Vero-E6, BHK-21, THP-1 cell line and RAW 264.7 cells) were assessed. Surprisingly, it was found that the human monocyte cells THP-1 and murine macrophage cell line RAW 264.7 were permissive to all the SARS-CoV-2 isolates. The neutralization susceptibility of viral isolates to vaccine-induced antibodies was determined using sera from individuals vaccinated in the Government run vaccine drive in India. The micro-neutralization assay suggested that both Covaxin and Covishield vaccines were equally effective (100% neutralization) against all of the isolates. The whole genome sequencing of culture adapted viral isolates and viral genome from patient oropharyngeal swab sample suggested that repetitive passaging of SARS-CoV2 virus in Vero-E6 cells did not lead to emergence of many mutations during the adaptation in cell culture. Phylogenetic analyses revealed that the five isolates clustered to respective clades. The major goal was to isolate and adapt SARS-CoV-2 viruses in in-vitro cell culture with minimal modification to facilitate research activities involved in understanding the molecular virology, host-virus interactions, application of these strains for drug discovery and animal challenge models development which eventually will contribute towards the development of effective and reliable therapeutics.

microbiology↗
bioRxiv2021

Comparative secretomics identifies conserved WAxR motif-containing effectors in rust fungi that suppress cell death in plants

Identification of novel effectors with conserved features has always remained a challenge in plant-pathogen interaction studies. The introduction of the genomics era in plant-pathogen studies has led to the identification of significant candidate effectors with novel motifs such as RxLR and dEER motifs. However, in the case of fungal pathogens, limited conserved motifs associated with effectors have been discovered yet. In the present study, we have performed comparative secretome analysis for major plant pathogens of diverse nutrition mechanisms with the aim of dissecting the features underlying their corresponding secretome and conserved motifs. We showed that rust fungi possess the lowest Cell wall degrading enzymes (CWDEs) consortium lower than other biotrophic pathogens. We also showed rust fungi possess the highest secretory superoxide dismutase (SOD) than other studied plant pathogens. Further, we prioritized the candidate secretory effectors proteins (CSEPs) of all the studied pathogens by combining various effector mining parameters to highlight the candidates with potential effector features. A novel WAxR motif in conjugation with the Y/F/WxC (FGC) motif was identified in the effectors of various P. striiformis races present globally. The WAxR/WAxR like motifs ( WxxR, WAxx, xAxR) containing effectors were also found in the secretome of other rust fungi. Further, the functional validation of two candidate effectors with WAxR motif from P. striiformis Yr9 showed that these effectors localize to the nucleus as well as cytoplasm, and are able to suppress BAX induced cell death in Nicotiana benthamiana. The mutation analysis of individual residues of the WAxR motif (W, A, R) however did not affect the cell death suppression nor subcellular localization of these effectors. Overall, the current study reports the presence of novel motifs in large numbers of effectors of rust fungi with cell death suppression features. HighlightsO_LISecretome analysis of various plant pathogens performed C_LIO_LIA prioritization list for candidate effectors designed C_LIO_LIA novel WAxR motif was discovered in rust fungal effector proteins C_LIO_LITwo WAxR candidate effectors were functionally validated C_LI

microbiology↗
bioRxiv2021

Horizontal transfer of a conserved npc-2 like effector gene in rust fungi that suppresses cell death in plants

ML/MD-2 is a conserved lipid/sterol-binding protein family having a role in sterol transfer and innate immunity in lower and higher eukaryotes. Here we report a genome-wide survey of this family, identifying 84 genes in 25 fungal and five oomycetes plant pathogen, having a different nutrition mode. All the fungal species were found to have varied numbers of family members, a distinctively substantial expansion of the ML gene family was observed in Rhizophagus irregularis (RI) with 33 genes. Our analysis also showed that NPC2 like proteins, a subfamily of ML domain superfamily, were not only restricted to animals and insect species but also present in plant fungal pathogens, including members of Clavicipitaceae, Pucciniacease, and Tremellaceae family. The phylogenetic analysis showed that these NPC2 like fungal proteins are more closely related to animals/insects than other fungal species. The molecular docking studies of these proteins with cholesterol and other derivatives indicate lipid-binding functional conservation across the animal and fungi kingdom. Further, the full length CDS of one of the npc2 like genes from Puccinia triticina (Pt5643) was PCR amplified and further characterized using various studies such as qRT-PCR, expression in onion epidermal cells, Nicotiana benthamiana for subcellular localization studies, yeast functional complementation, and expression studies. The mRNA abundance of Pt5643 was observed to be increased along with the infection progression and exhibits the highest expression at 5thday post-infection (dpi), suggesting its important role in the P. triticina infection cycle in wheat. The fluorescent confocal microscopy of transiently expressed YFP tagged Pt5643 in onion epidermal cells and N. benthamiana shows its location in cytoplasm and nucleus, indicating its involvement in the manipulation of host genes. The functional complementation of Pt5643 in npc2 mutant yeast showed its functional similarity to the eukaryotic npc2 gene. Further, the overexpression of Pt5643 also suppressed the BAX and H2O2 induced program cell death in N. benthamiana and yeast, respectively thus proving to be a novel horizontally transferred effector in rust fungal pathogens. Altogether the present study reports the novel function of fungal NPC2 like proteins playing a crucial role in host defense manipulation possibly through lipid binding/transport similar to animals.

microbiology↗
bioRxiv2021

Unraveling the regulatory role of miRNAs responsible for proanthocyanidin biosynthesis in the underutilized legume Psophocarpus tetragonolobus (L.) DC.

The underutilized legume winged bean (Psophocarpus tetragonolobus (L.) DC.) is deposited with various degrees of proanathocyanidin (PA) or condensed tannin (CT) on its seed-coat. PA content of two different lines of P. tetragonolobus was estimated and accordingly they were denoted as high-proanthocyanidin containing winged bean (HPW) and low-proanthocyanidin containing winged bean (LPW). The level of PA-content varied as 59.23 mg/g in HPW and 8.68 mg/g in LPW when estimated through vanillin-HCl assay. The identification and quantification of catechin and epigallocatechin gallate were estimated in a range of 63.8 mg/g and 2.3mg/g respectively in HPW whereas only epigallocatechin gallate was reported in LPW line with a value of 3 mg/g. A comparative miRNA profiling of the leaf-tissues of these contrasting lines of P. tetragonolobus revealed a total of 139 mature miRNAs. Isoforms of known novel miRNAs were also identified in this study. Differentially expressed miRNAs e.g., miR156, miR396, miR4414b, miR4416c, miR894, miR2111 and miR5139 were validated through qRT-PCR analysis. Target prediction of the identified miRNAs especially miR156, miR396, miR4416b shows that they have a potential role in the proanthocyanidin biosynthesis of P. tetragonolobus. The study will provide the basis for understanding the role of miRNAs in regulating the biosynthesis of proanthocyanidin.

genomics↗
bioRxiv2021

Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host-factors having implication in the disease pathogenesis and severity

Syrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests lung pathology that resembles human COVID-19 patients. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. The findings of this study confirm the infectivity of this isolate in vivo. Analysis of clinical parameters and tissue samples shows a similar type of pathophysiological manifestation of SARS-CoV-2 infection as reported earlier in COVID-19 patients and hamsters infected with other isolates. The lung-associated pathological changes were very prominent on the 4th day post-infection (dpi), mostly resolved by 14dpi. Here, we carried out quantitative proteomic analysis of the lung tissues from SARS-CoV-2-infected hamsters at day 4 and day 14 post infection. This resulted in the identification of 1,585 differentially expressed proteins of which 68 proteins were significantly altered among both the infected groups. Pathway analysis revealed complement and coagulation cascade, platelet activation, ferroptosis and focal adhesion as the top enriched pathways. In addition, we also identified altered expression of two pulmonary surfactant-associated proteins (Sftpd and Sftpb), known for their protective role in lung function. Together, these findings will aid in the identification of candidate biomarkers and understanding the mechanism(s) involved in SARS-CoV-2 pathogenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=143 HEIGHT=200 SRC="FIGDIR/small/434371v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1930556org.highwire.dtl.DTLVardef@14376d6org.highwire.dtl.DTLVardef@2f064eorg.highwire.dtl.DTLVardef@1472572_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗
bioRxiv2021

Unravelling cotton RNAseq repositories to the fiber development specific modules and their alliance with the fiber-related traits

Cotton fiber development is still an intriguing question to understand the fiber commitment and development. Here, we remapped >350 publicly available cotton RNA sequencing data on recently published cotton genome with [~]400 fold coverage. The differentially expressed genes were clustered in six modules whose functions are specific to commitment, initiation, elongation and Secondary Cell Wall (SCW) fiber development stages. Gene Ontology analysis of commitment and initiation specific modules suggests enrichment of genes involved in organ development. The modules specific for elongation and SCW showed significant enrichment of hydroxyproline-rich proteins and hydrolases. Transcription factors (TFs) binding frequency of defined modules suggested that homeodomain, MYB and NAC expresses at commitment stages but their expression was governed by other TFs. We also mined the stage-specific transcriptional biomarker and Exclusively Expressed Transcripts (EETs) for fiber. These EETs were positively selected during fiber evolution and cotton domestication. The extensive expression profiling of six EETs in 100 cotton genotypes at different fiber developmental stages using nCounter assay and their correlation with eight fiber-related suggests that several EETs are correlated with different fiber quality-related traits. Thus, our study reveals several important genes and pathways that may be important for cotton fiber development and future improvement of cotton.

plant biology↗
bioRxiv2020

Molecular basis of the logical evolution of the novel coronavirus SARS-CoV-2: A comparative analysis

A novel disease, COVID-19, is sweeping the world since end of 2019. While in many countries, the first wave is over, but the pandemic is going through its next phase with a significantly higher infectability. COVID-19 is caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that seems to be more infectious than any other previous human coronaviruses. To understand any unique traits of the virus that facilitate its entry into the host, we compared the published structures of the viral spike protein of SARS-CoV-2 with other known coronaviruses to determine the possible evolutionary pathway leading to the higher infectivity. The current report presents unique information regarding the amino acid residues that were a) conserved to maintain the binding with ACE2 (Angiotensin-converting enzyme 2), and b) substituted to confer an enhanced binding affinity and conformational flexibility to the SARS-CoV-2 spike protein. The present study provides novel insights into the evolutionary nature and molecular basis of higher infectability and perhaps the virulence of SARS-CoV-2.

evolutionary biology↗
bioRxiv2020

Unique mutational changes in SARS-CoV2 genome of different state of India

COVID-19 is a global pandemic causing more than 8 million deaths till mid-August, 2020. In India, more than 3 million confirmed cases have been reported although with relatively low death rate of 1.8%. In this study, we sequenced 47 genomes of SARS-CoV-2 from the patients of 13 districts of Uttar Pradesh (UP), the largest state of India using third-generation sequencing technique. The phylogenetic clustering revealed that no UP sample was aligned with the previously defined USA clade, where the mortality was high. We identified 56 distinct SNP variations in the genomes of UP resulting in a unique mutation rate of 1.19% per sequence, which is greater than the value 0.88% obtained for the rest of India. The relatively less death rate in UP indicates that the mutation in the virus is deleterious. Further investigation is required with larger sample size to determine the degree of virulence vis-a-vis SNP variation.

bioinformatics↗
bioRxiv2020

SARS-CoV2 genome analysis of Indian isolates and molecular modelling of D614G mutated spike protein with TMPRSS2 depicted its enhanced interaction and virus infectivity

COVID-19 that emerged as a global pandemic is caused by SARS-CoV-2 virus. The virus genome analysis during disease spread reveals about its evolution and transmission. We did whole genome sequencing of 225 clinical strains from the state of Odisha in eastern India using ARTIC protocol-based amplicon sequencing. Phylogenetic analysis identified the presence of all five reported clades 19A, 19B, 20A, 20B and 20C in the population. The analyses revealed two major routes for the introduction of the disease in India i.e. Europe and South-east Asia followed by local transmission. Interestingly, 19B clade was found to be much more prevalent in our sequenced genomes (17%) as compared to other genomes reported so far from India. The haplogroup analysis for clades showed evolution of 19A and 19B in parallel whereas the 20B and 20C appeared to evolve from 20A. Majority of the 19A and 19B clades were present in cases that migrated from Gujarat state in India suggesting it to be one of the major initial points of disease transmission in India during month of March and April. We found that with the time 20A and 20B clades evolved drastically that originated from central Europe. At the same time, it has been observed that 20A and 20B clades depicted selection of four common mutations i.e. 241 C>T (5UTR), P323L in RdRP, F942F in NSP3 and D614G in the spike protein. We found an increase in the concordance of G614 mutation evolution with the viral load in clinical samples as evident from decreased Ct value of spike and Orf1ab gene in qPCR. Molecular modelling and docking analysis identified that D614G mutation enhanced interaction of spike with TMPRSS2 protease, which could impact the shedding of S1 domain and infectivity of the virus in host cells.

genomics↗
bioRxiv2019

Autoimmunity Risk Gene IRGM is a Master Negative Regulator of Interferon Response by Controlling the Activation of cGAS STING and RIG-I-MAVS Signaling Pathways

Activation of type 1 interferon response is extensively connected with the antiviral immunity and pathogenesis of autoimmune diseases. Here, we found that IRGM, whose deficiency is linked with the genesis of several autoimmune disorders, is a master negative regulator of the interferon response. Mechanistically, we show that IRGM interacts with nucleic acid sensor proteins, including cGAS and RIG-I, and mediates their autophagic degradation to restrain activation of interferon signaling. Further, IRGM maintains mitophagy flux, and its deficiency results in the accumulation of defunct leaky mitochondria that releases cytosolic DAMPs triggering activation of interferon responses via cGAS-STING and RIG-I-MAVS signaling axis. Due to an enduring type 1 IFN response in IRGM-deficient cells and mice, they were intrinsically resistant to infection of the Japanese Encephalitis virus, Herpes Simplex virus, and Chikungunya virus. Altogether, this study defines the molecular mechanisms by which IRGM maintains interferon homeostasis and protects from autoimmune diseases. Further, it identifies IRGM as a broad therapeutic target for defense against viruses.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC=\"FIGDIR/small/815506v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (48K):\norg.highwire.dtl.DTLVardef@1d4822org.highwire.dtl.DTLVardef@6aebbcorg.highwire.dtl.DTLVardef@19a9b72org.highwire.dtl.DTLVardef@1539195_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗