IL12 and viral infection

BACKGROUND: The varicella-zoster virus (VZV), belonging to the group of human α-herpesviruses, has yet to be developed as a platform for oncolytic virotherapy, despite indications from clinical case reports suggesting a potential association between VZV infection and cancer remission. METHODS: Here, we constructed oncolytic VZV candidates based on the vaccine strain vOka and the laboratory strain Ellen. These newly engineered viruses were subsequently assessed for their oncolytic properties in the human MeWo melanoma xenograft model and the mouse B16-F10-nectin1 melanoma syngeneic model...

Monkeypox virus (MPXV) infections in humans cause neurological disorders while studies of MPXV-infected animals indicate that the virus penetrates the brain. Pyroptosis is an inflammatory type of regulated cell death, resulting from plasma membrane rupture (PMR) due to oligomerization of cleaved gasdermins to cause membrane pore formation. Herein, we investigated the human neural cell tropism of MPXV compared to another orthopoxvirus, vaccinia virus (VACV), as well as its effects on immune responses and cell death...

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin...

Tuberculosis (TB), an infection caused by Mycobacterium tuberculosis (Mtb) , is one of the primary causes of death globally. The treatment of TB is long and based on several drugs, producing problems in compliance and toxicity, increasing Mtb resistance to first-line antibiotics that result in multidrug-resistant TB and extensively drug-resistant TB. Thus, the need for new anti-TB treatments has increased. Here, we review some model strategies to study gene therapy based on the administration of a recombinant adenovirus that encodes diverse cytokines, such as IFNγ, IL12, GM/CSF, OPN, TNFα, and antimicrobial peptides to enhance the protective immune response against Mtb ...

Dominant negative mutations in CARD11 have been reported in patients with immune dysregulation, severe atopic features, and variable T cell alterations. Data on Natural killer (NK) cells from affected patients are lacking. We report on a 12-year-old boy with severe atopic dermatitis, food induced anaphylaxis and hypogammaglobulinemia harbouring a novel de novo heterozygous variant c.169G > A; p.Glu57Lys in CARD11. The dominant negative effect of this mutation was confirmed on both CD4+ and CD8+ ...

The proprotein convertase subtilisin/kexins (PCSKs) regulate biological actions by cleaving immature substrate proteins. The archetype PCSK, FURIN, promotes the pathogenicity of viruses by proteolytically processing viral proteins. FURIN has also important regulatory functions in both innate and adaptive immune responses but its role in the CD8+ CTLs remains enigmatic. We used a T cell specific FURIN deletion in vivo to demonstrate that FURIN promotes host response against the CTL-dependent lymphocytic choriomeningitis virus by virtue of restricting viral burden and augmenting IFNG production...

Regulatory T (Treg ) cells are an immunosuppressive population that are required to maintain peripheral tolerance and prevent tissue damage from immunopathology, via anti-inflammatory cytokines, inhibitor receptors and metabolic disruption. Here we show that Treg cells acquire an effector-like state, yet remain stable and functional, when exposed to interferon gamma (IFNγ) during infection with lymphocytic choriomeningitis and influenza A virus. Treg cell-restricted deletion of the IFNγ receptor (encoded by Ifngr1), but not the interleukin 12 (IL12) receptor (encoded by Il12rb2), prevented TH 1-like polarization (decreased expression of T-bet, CXC motif chemokine receptor 3 and IFNγ) and promoted TH 2-like polarization (increased expression of GATA-3, CCR4 and IL4)...

BACKGROUND: The transmembrane protease serine 2 (TMPRSS2) proteolytically activates the envelope proteins of several viruses for viral entry via membrane fusion and is therefore an interesting and promising target for the development of broad-spectrum antivirals. However, the use of a host protein as a target may lead to potential side effects, especially on the immune system. We examined the effect of a genetic deletion of TMPRSS2 on dendritic cells. METHODS: Bone marrow cells from wild-type (WT) and TMPRSS2-deficient mice (TMPRSS2-/- ) were differentiated to plasmacytoid dendritic cells (pDCs) and classical DCs (cDCs) and activated with various toll-like receptor (TLR) agonists...

UNLABELLED: Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0...

BACKGROUND: The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection, and constitutes the viral component of mRNA-based COVID-19 vaccines...

Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. Equus caballus papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription factors...

BACKGROUND: HER2-based retargeted viruses are in advanced phases of preclinical development of breast cancer models. Mesothelin (MSLN) is a cell-surface tumor antigen expressed in different subtypes of breast and non-breast cancer. Its recent identification as a marker of some triple-negative breast tumors renders it an attractive target, presently investigated in clinical trials employing antibody drug conjugates and CAR-T cells. The availability of MSLN-retargeted oncolytic viruses may complement the current immunotherapeutic panel of biological drugs against HER2-negative breast and non-breast tumors...

Influenza A virus (IAV)-specific CD8+ T-cell response was shown to provide protection against pandemic and seasonal influenza infections. However, the response was often relatively weak and the mechanism was unclear. Here, we show that the composition of IAV released from infected cells is regulated by the neuraminidase (NA) activity and the cells infected by NA-defective virus cause intracellular viral protein accumulation and cell death. In addition, after uptake of NA-defective viruses by dendritic cells (DCs), an expression of the major histocompatibility complex class I is induced to activate IAV-specific CD8+ T-cell response...

The progress in the understanding of the pathophysiology of rheumatic diseases provided a rational basis for the development of biologic disease‑modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), which have completely revolutionized the treatment of inflammatory conditions. These agents differ in terms of their effectiveness for controlling specific rheumatic diseases depending on the pivotal cytokine driving the inflammatory process. Cytokine blockers were the first to be developed and rapidly expanded...

Triple-negative breast cancer (TNBC) is a difficult-to-treat disease with high rates of local recurrence, distant metastasis, and poor overall survival with existing therapies. Thus, there is an unmet medical need to develop new treatment regimen(s) for TNBC patients. An oncolytic herpes simplex virus encoding a master anti-tumor cytokine, interleukin 12, (designated G47Δ-mIL12) selectively kills cancer cells while inducing anti-tumor immunity. G47Δ-mIL12 efficiently infected and killed murine (4T1 and EMT6) and human (HCC1806 and MDA-MB-468) mammary tumor cells in vitro ...

Coronavirus disease 2019 or COVID-19 has rapidly emerged as a global pandemic. This viral infection involves the upper respiratory tract and could lead to severe pneumonia with respiratory distress or even death. Certain studies have found higher initial plasma levels of most pro-inflammatory cytokines during the course of the infection. In this context, both in vitro and in vivo studies have revealed that metronidazole could decrease the levels of several cytokines, which are known to increase during the COVID-19 infection, including interleukin (IL)8, IL6, IL1B, tumor necrosis factor (TNF)α, IL12, IL1α, and interferon (IFN)γ, as well as the levels of C-reactive protein (CRP) and neutrophil count...

RIG-I is a cytosolic RNA sensor that recognizes short 5' triphosphate RNA, commonly generated during virus infection. Upon activation, RIG-I initiates antiviral immunity, and in some circumstances, induces cell death. Because of this dual capacity, RIG-I has emerged as a promising target for cancer immunotherapy. Previously, a sequence-optimized RIG-I agonist (termed M8) was generated and shown to stimulate a robust immune response capable of blocking viral infection and to function as an adjuvant in vaccination strategies...

Epstein-Barr virus (EBV) initiates various immune disorders, including changes in cytokine profile, which result in the development of different pathological conditions, in particular, allergopathology. Aim - to investigate the level of cytokines with antiviral activity in patients with allergopathology in active and latent phases of chronic persistence of Epstein-Barr viral infection. In general, 38 patients with allergopathology in combination with chronic persistence of EBV-infection in active (1st group) and latent (2nd group) phases were examined...

Treatment of psoriasis and psoriatic arthritis in patients with concomitant chronic, severe viral infections, particularly HIV or HBV, represents a challenge, due to contraindication to conventional immunomodulating systemic drugs and biologics, including anti-TNF alpha, anti-IL12/23, and anti-IL17 agents. Recently, apremilast, a selective inhibitor of phosphodiesterase E4 has been suggested to be a safe and effective therapeutic option in HIV-infected population with psoriatic arthritis. We report the case of a patient with psoriatic arthritis and concomitant HIV and HBV infection successfully treated with apremilast...

Dear Editor, Eczema is an inflammatory dermatitis mediated by cellular immunity, with an etiology in which environmental, immunological, and genetic factors are involved. Skin inflammation through proinflammatory cytokines creates a favorable environment for microbial antigens and optimal conditions for infection (1). In case of underlying immunosuppression, inflammatory features of dermatitis and superimposed infections are more severe. The presence of minor trauma of the skin in the form of fissures can favor both easier inoculation of some bacterial germs, leading to a dermatitis superinfection, and/or the transcutaneous inoculation of atypical mycobacteria, with a possibility of developing localized types of tuberculous lymphadenitis (TLA)...