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Alphaviruses: Host pathogenesis, immune response, and vaccine & treatment updates.

J Gen Virol 2021 08;102(8)

Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.

Human pathogens belonging to the genus, in the family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and polyarthralgia, defined as joint pain and inflammation, as well as encephalitis. In the last decade, our understanding of the interactions between members of the alphavirus genus and the human host has increased due to the re-appearance of the chikungunya virus (CHIKV) in Asia and Europe, as well as its emergence in the Americas. Read More

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Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1-dependent inhibition of the NLRP3 inflammasome in an EAP mouse model.

Prostate 2021 Nov 21;81(15):1179-1190. Epub 2021 Aug 21.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). Read More

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November 2021

T cell homeostatic proliferation promotes a redox state that drives metabolic and epigenetic upregulation of inflammatory pathways in lupus.

Antioxid Redox Signal 2021 Jul 30. Epub 2021 Jul 30.

University of Vermont College of Medicine, 12352, Burlington, Vermont, United States;

Significance: Numerous abnormalities in T cells have been described in patients with systemic lupus erythematosus (SLE), including lymphopenia, DNA demethylation, expression of endogenous retroviruses, increased cell death, enlarged mitochondria, production of reactive oxygen species (ROS), and the appearance of CD4-CD8- T cells. We propose a model in which accelerated homeostatic proliferation of T cells promotes an epigenetic and metabolic program leading to this cluster of abnormalities. Recent Advances: Growing knowledge of the innate immune disorders in SLE has included increased mitochondrial size and ROS production that induces oligomerization of mitochondrial antiviral-signaling (MAVS) protein and type I Interferon production, as well as DNA demethylation, upregulation of inflammatory genes, and expression of certain endogenous retroviruses in SLE peripheral blood mononuclear cells (PBMC). Read More

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Evaluation of possible prophylactic and therapeutic effect of mefloquine on experimental cryptosporidiosis in immunocompromised mice.

J Parasit Dis 2021 Jun 13;45(2):380-393. Epub 2020 Nov 13.

Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Cryptosporidiosis is an imperative global health concern. Unfortunately, Nitazoxanide (NTZ) (the nowadays drug of choice) is not effective in treatment of immunocompromised patients. We aimed to assess the possible anti-cryptosporidial prophylactic and therapeutic effects of Mefloquine (MQ) on infected immunosuppressed murine models. Read More

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Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells.

Int J Mol Sci 2021 Jun 26;22(13). Epub 2021 Jun 26.

Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, Russia.

The search for and analysis of new ligands for innate immunity receptors are of special significance for understanding the regulatory mechanisms of immune response. Here we show that the major heat shock protein 70 (Hsp70) can bind to and activate TREM-1, the innate immunity receptor expressed on monocytes. The Hsp70-TREM-1 interaction activates expression of TNFα and IFNγ mRNAs in monocytes and stimulates IL-2 secretion by PBMCs. Read More

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Hepatic pathological features in naïve patients with chronic hepatitis C who have developed thyroid disorder.

Rom J Morphol Embryol 2020 Oct-Dec;61(4):1085-1097

Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania;

Knowing the hepatic pathological features encountered in patients with chronic hepatitis C (CHC) and the fact that extrahepatic manifestations occur only in people with certain characteristics of the immune system, we tried to evaluate, qualitatively and semi-quantitatively, the liver pathological aspects encountered in 96 patients with CHC, previously untreated with Interferon (naïve), who showed or did not show signs of thyroid disorder (TD), hospitalized in the 2nd Medical Clinic of the Emergency County Hospital, Craiova, Romania, within a period of five years (2007-2012). Following hormonal, immunological, and thyroid ultrasound investigations, 14 (14.58%) of the 96 patients showed signs of TD. Read More

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Phenotypic overlap between atopic dermatitis and autism.

BMC Neurosci 2021 Jun 22;22(1):43. Epub 2021 Jun 22.

Dept. of Dermatology, University of California, NCIRE, and Veterans Affairs Medical Center, 4150 Clement Street, MS 190, San Francisco, CA, 94121, USA.

Background: Autism, a childhood behavioral disorder, belongs to a large suite of diseases, collectively referred to as autism spectrum disorders (ASD). Though multifactorial in etiology, approximately 10% of ASD are associated with atopic dermatitis (AD). Moreover, ASD prevalence increases further as AD severity worsens, though these disorders share no common causative mutations. Read More

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Pulmonary alveolar proteinosis complicated with tuberculosis: A case report.

World J Clin Cases 2021 Jun;9(17):4400-4407

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of phospholipoproteinaceous material in the alveoli. Cases of PAP complicated with tuberculosis are much more complex and have rarely been well recorded.

Case Summary: We describe a 21-year-old Han Chinese patient with suspicious lung infection associated with mild restrictive ventilatory dysfunction and diffusion reduction. Read More

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Coronavirus Disease 2019 in Children.

Front Pediatr 2021 28;9:668484. Epub 2021 May 28.

Section of Pediatrics, Pediatric Pulmonology Unit, Department of Translational Medical Sciences, Università di Napoli Federico II, Naples, Italy.

Since its appearance in Wuhan in mid-December 2019, acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related 19 coronavirus disease (COVID-19) has spread dramatically worldwide. It soon became apparent that the incidence of pediatric COVID-19 was much lower than the adult form. Morbidity in children is characterized by a variable clinical presentation and course. Read More

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An Impaired Inflammatory and Innate Immune Response in COVID-19.

Authors:
Sung Ho Park

Mol Cells 2021 Jun;44(6):384-391

Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. Read More

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Transcriptome analysis reveals a complex response to the RGNNV/SJNNV reassortant Nervous Necrosis Virus strain in sea bream larvae.

Fish Shellfish Immunol 2021 Jul 7;114:282-292. Epub 2021 May 7.

Department of Comparative Biomedicine and Food Science, University of Padova, Viale Dell'Università, 16 35020, Legnaro, PD, Italy.

The gilthead sea bream (Sparus aurata) is a marine fish of great importance for Mediterranean aquaculture. This species has long been considered resistant to Nervous Necrosis Virus (NNV), an RNA virus that causes massive mortalities in several farmed fish animals. However, the recent appearance of RGNNV/SJNNV reassortant strains started to pose a serious threat to sea bream hatcheries, as it is able to infect larvae and juveniles of this species. Read More

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Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE.

Arthritis Res Ther 2021 04 30;23(1):132. Epub 2021 Apr 30.

Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM).

Methods: Skin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Read More

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Proteasome subunit beta type-8 from sevenband grouper negatively regulates cytokine responses by interfering NF-κB signaling upon nervous necrosis viral infection.

Fish Shellfish Immunol 2021 Jun 13;113:118-124. Epub 2021 Apr 13.

Department of Aqualife Medicine, Chonnam National University, Yeosu, Republic of Korea. Electronic address:

During viral infection, proper regulation of immune signaling is essential to ensure successful clearance of virus. Immunoproteasome is constitutively expressed and gets induced during viral infection by interferon signaling and contributes to regulate proinflammatory cytokine production and activation of the NF-κB pathway. In this study, we identified Hs-PSMB8, a member of the proteasome β-subunits (PSMB) family, as a negative regulator of NF-κB responses during NNV infection. Read More

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Dermoscopic Features of Giant Molluscum Contagiosum in a Patient with Acquired Immunodeficiency Syndrome.

Acta Dermatovenerol Croat 2020 Dec;28(7):233-235

Martyna Sławińska MD, PhD, Department of Dermatology, Venereology and Allergology Medical University of Gdańsk, Smoluchowskiego 17 Street, 80-214 Gdańsk;

Giant molluscum contagiosum (MC) is a peculiar variant of the disease with the presence of multiple or single lesions larger than 5 mm. In contrast to typical molluscum contagiosum, dermoscopic features of giant lesions have been poorly described, and none of the reports included multiple giant lesions in an immunocompromised patient. We present a patient with acquired immunodeficiency syndrome diagnosed with multiple giant molluscum contagiosum along with the dermoscopic features of this entity. Read More

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December 2020

Erdheim-Chester disease: an unusual aetiology of bilateral lipomatous perinephric masses.

BMJ Case Rep 2021 Apr 7;14(4). Epub 2021 Apr 7.

Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

A 53-year-old man presented with a history of progressive abdominal distention for 1 year. Physical examination revealed large palpable masses in the bilateral flank regions. Contrast-enhanced CT of the abdomen showed bilateral, symmetrical large perinephric masses with fat attenuating areas, which was further confirmed on MRI. Read More

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Rapid Induction of Pulmonary Inflammation, Autoimmune Gene Expression, and Ectopic Lymphoid Neogenesis Following Acute Silica Exposure in Lupus-Prone Mice.

Front Immunol 2021 23;12:635138. Epub 2021 Feb 23.

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States.

Occupational exposure to crystalline silica (cSiO) is etiologically associated with systemic lupus erythematosus (lupus) and other autoimmune diseases. cSiO's autoimmune effects in humans can be mimicked chronically in female lupus-prone NZBWF1 mice following repeated exposure to the particle. However, the immediate and short-term effects of cSiO in this widely used model of autoimmune disease are not well-understood. Read More

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September 2021

Pathophysiology of Skin Resident Memory T Cells.

Front Immunol 2020 3;11:618897. Epub 2021 Feb 3.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Tissue resident memory T (T) cells reside in peripheral, non-lymphoid tissues such as the skin, where they act as alarm-sensor cells or cytotoxic cells. Physiologically, skin T cells persist for a long term and can be reactivated upon reinfection with the same antigen, thus serving as peripheral sentinels in the immune surveillance network. CD8CD69CD103 T cells are the well-characterized subtype that develops in the epidermis. Read More

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A Phase I/II Clinical Trial to evaluate the efficacy of baricitinib to prevent respiratory insufficiency progression in onco-hematological patients affected with COVID19: A structured summary of a study protocol for a randomised controlled trial.

Trials 2021 Feb 5;22(1):116. Epub 2021 Feb 5.

Intensive Care Department, Hospital Universitari de Bellvitge, L'Hospitalet de LL., Barcelona, Spain.

Objectives: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. Read More

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February 2021

Evaluating the Role of STAT3 in CD4 T Cells in Susceptibility to Invasive Aspergillosis.

Infect Immun 2021 04 16;89(5). Epub 2021 Apr 16.

Transplant Infectious Diseases, Ajmera Transplant Center, University Health Network, University of Toronto, Toronto, Canada

We aimed to determine whether T cell-specific STAT3 deletion influences the immune response to in the immunosuppressed context in CD4 mice. Immunosuppressed and nonimmunosuppressed CD4 mice and littermate Stat3 (Stat3) mice were infected with in an aerosol chamber, and the weight, activity, appearance, and respiratory rate of the mice were monitored daily for 21 days to evaluate their survival. infection was confirmed by lung fungal culture counts, histology, and a galactomannan test. Read More

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Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity.

Proc Natl Acad Sci U S A 2021 02;118(6)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.

Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate and severe COVID-19. We provide a deep and comprehensive map of the MNP landscape in COVID-19. Read More

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February 2021

How to Survive COVID-19 Even If the Vaccine Fails.

Authors:
Andrea D Branch

Hepatol Commun 2020 Dec 5;4(12):1864-1879. Epub 2020 Nov 5.

Division of Liver Diseases Department of Medicine Icahn School of Medicine at Mount Sinai New York NY.

Coronavirus disease 2019 (COVID-19) has created an emergency of epic proportions. While a vaccine may be forthcoming, this is not guaranteed, as discussed herein. The potential problems and ominous signs include (1) lung injury that developed in animals given an experimental vaccine for the severe acute respiratory syndrome coronavirus (SARS-CoV)-1; (2) a perversion of adaptive immune responses called antibody-dependent enhancement of infection that occurs in SARS-CoV-1 and that may occur in people vaccinated for COVID-19; (3) the frequent and recurrent infections that are caused by respiratory coronaviruses; and (4) the appearance of mutations in SARS-CoV-2 proteins, which raise the specter of vaccine escape mutants. Read More

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December 2020

Cytokines TNFα, IFNγ and IL-2 Are Responsible for Signal Transmission from the Innate Immunity Protein Tag7 (PGLYRP1) to Cytotoxic Effector Lymphocytes.

Cells 2020 12 4;9(12). Epub 2020 Dec 4.

Laboratory of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, Vavilova 34/5, 111394 Moscow, Russia.

Studies on the mechanisms of activation of cytotoxic lymphocyte subpopulations are an important research direction in modern immunology. This study provides a detailed analysis of the effect of Tag7 (PGRP-S, PGLYRP1) on the development of lymphocyte subpopulations cytotoxic against MHC-negative tumor cells in a pool of peripheral blood mononuclear cells (PBMCs). The results show that Tag7 can bind to the TREM-1 receptor on the surfaces of monocytes, thereby triggering the expression of mRNA TNFα and IFNγ. Read More

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December 2020

Inhibitory effects of recombinant porcine interferon-α on porcine transmissible gastroenteritis virus infections in TGEV-seronegative piglets.

Vet Microbiol 2021 Jan 17;252:108930. Epub 2020 Nov 17.

Department of Microbiology, Anhui Medical University, Hefei, Anhui Province, 230032, PR China; Anhui Jiuchuan Biotechnology Co., Ltd., Wuhu, Anhui, PR China; Wuhu Overseas Students Pioneer Park, Wuhu, Anhui, PR China. Electronic address:

Our previous research obtained purified recombinant porcine interferon-α (rPoIFN-α) containing thioredoxin (Trx) fusion tag in E. coli Rosetta (DE3). Here, we evaluate the efficacy of this rPoIFN-α to prevent piglets from the infection of the transmissible gastroenteritis virus (TGEV) attack. Read More

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January 2021

Phosphoproteomics identifies microglial Siglec-F inflammatory response during neurodegeneration.

Mol Syst Biol 2020 12;16(12):e9819

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Alzheimer's disease (AD) is characterized by the appearance of amyloid-β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK-p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec-F which was upregulated on a subset of reactive microglia. Read More

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December 2020

Pathogenicity and Immune Responses in Specific-Pathogen-Free Chickens During Fowl Adenovirus Serotype 4 Infection.

Avian Dis 2020 09;64(3):315-323

College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.

Hydropericardium-hepatitis syndrome, a recently emerged disease of chickens, is caused by some strains of fowl adenovirus serotype 4 (FAdV-4). However, the relationship between the immune response and cytokine expression during FAdV-4 infection is largely unknown. In this study, our data showed that all chickens exhibited typical clinical signs and lesions and that the viral load was significantly increased in both the liver and thymus following FAdV-4 infection. Read More

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September 2020

Interferon lambda 4 gene polymorphisms as a predicting tool of response to hepatitis C virus genotype 4 patients treated with Sofosbuvir and Ribavirin.

Infect Genet Evol 2020 12 28;86:104606. Epub 2020 Oct 28.

Department of Zoology, Physiology Division, Faculty of Science, Beni-Suef University, Egypt.

The relation between interferon lambda 4 gene (IFNL4) and direct acting antiviral (DAA) regimens in hepatitis C virus (HCV) infected patients is not clear. So, a single nucleotide polymorphisms (SNP) of IFNL4 gene genotypes and its relationship with Sofosbuvir (SOF) and Ribavirin (RBV) treatment response is under consideration. This study aims to investigate the relation between IFNL4 polymorphisms and clearance of HCV genotype 4 for HCV patients. Read More

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December 2020

Endogenous HLA-DQ8αβ programs superantigens (SEG/SEI) to silence toxicity and unleash a tumoricidal network with long-term melanoma survival.

J Immunother Cancer 2020 10;8(2)

Biomedical Sciences, Universtiy of North Dakota School of Medicine, Grand Forks, North Dakota, USA.

Background: As the most powerful T cell agonists known, superantigens (SAgs) have enormous potential for cancer immunotherapy. Their development has languished due to high incidence (60%-80%) of seroreactive neutralizing antibodies in humans and tumor necrosis factor-α (TNFα)-mediated cardiopulmonary toxicity. Such toxicity has narrowed their therapeutic index while neutralizing antibodies have nullified their therapeutic effects. Read More

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October 2020

A Case of Steatocystoma Multiplex in a Psoriatic Patient during Treatment with Anti-IL-12/23.

Skin Appendage Disord 2020 Sep 14;6(5):309-311. Epub 2020 Jul 14.

Department of Dermatology, University of Naples Federico II, Naples, Italy.

Steatocystoma multiplex (SM) is an autosomal dominant disorder developing in adolescence or early adult age. The occurrence of multiple asymptomatic cutaneous cysts on the axillae, groin, trunk, and limbs characterizes the disease. SM is associated with a missense mutation in the keratin 17 gene (KRT17), a gene encoding for a type I intermediate filament (keratin 17 [K17]), mainly expressed in the epithelial appendages (hair follicles and sebaceous glands). Read More

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September 2020

Murine GFP-Mx1 forms nuclear condensates and associates with cytoplasmic intermediate filaments: Novel antiviral activity against VSV.

J Biol Chem 2020 12 19;295(52):18023-18035. Epub 2020 Oct 19.

Department of Medical Biotechnology, University School of Medical Sciences, Poznań, Poland; Department of Diagnostics and Immunology of Cancer, Greater Poland Cancer Center, Poznań, Poland.

Type I and III interferons induce expression of the "myxovirus resistance proteins" MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms structures, whereas murine Mx1 forms bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). Read More

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December 2020

High Smad7 in the early post-operative recurrence of Crohn's disease.

J Transl Med 2020 10 19;18(1):395. Epub 2020 Oct 19.

Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Roma, Italy.

Background: In Crohn's disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD.

Methods: Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Read More

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October 2020