Immunopathology of viral

Cardiomyopathy syndrome (CMS) caused by piscine myocarditis virus (PMCV) is a severe cardiac disease in Atlantic salmon (Salmo salar) and one of the leading causes of morbidity and mortality in the Norwegian aquaculture industry. Previous research suggest a variation in individual susceptibility to develop severe disease, however the role of the immune response in determining individual outcome of CMS is poorly understood particularly in cases where fish are also challenged by stress. The present study's aim was therefore to characterize cardiac transcriptional responses to PMCV infection in Atlantic salmon responding to infection under stressful conditions with a high versus low degree of histopathological damage...

OBJECTIVES: Antiretroviral therapy (ART) efficacy is jeopardized by the emergence of drug resistance mutations in HIV, compromising treatment effectiveness. This study aims to propose novel analogs of Effavirenz (EFV) as potential direct inhibitors of HIV reverse transcriptase, employing computer-aided drug design methodologies. METHODS: Three key approaches were applied: a mutational profile study, molecular dynamics simulations, and pharmacophore development. The impact of mutations on the stability, flexibility, function, and affinity of target proteins, especially those associated with NRTI, was assessed...

Vaccines have demonstrated remarkable effectiveness in protecting against COVID-19; however, concerns regarding vaccine-associated enhanced respiratory diseases (VAERD) following breakthrough infections have emerged. Spike protein subunit vaccines for SARS-CoV-2 induce VAERD in hamsters, where aluminum adjuvants promote a Th2-biased immune response, leading to increased type 2 pulmonary inflammation in animals with breakthrough infections. To gain a deeper understanding of the potential risks and the underlying mechanisms of VAERD, we immunized ACE2-humanized mice with SARS-CoV-2 Spike protein adjuvanted with aluminum and CpG-ODN...

COVID-19 is of special concern to immunocompromised individuals, including organ transplant recipients. However, the exact implications of COVID-19 for the immunocompromised host remain unclear. Existing theories regarding this matter are controversial and mainly based on clinical observations. Here, the postmortem histopathology, immunopathology, and viral presence in various tissues of a kidney transplant recipient with COVID-19 were compared to those of 2 nontransplanted patients with COVID-19 matched for age, sex, length of intensive care unit stay, and admission period in the pandemic...

OBJECTIVE(S): Comparative clinical and morphological characterization of lesions of the vascular and nervous system in cases of maternal death associated with COVID-19. STUDY DESIGN: The study included autopsy in 12 cases of maternal death with a positive intravital result for SARS-CoV-2 by reverse transcription polymerase chain reaction. For histopathology, tissue samples were taken from the internal organs of each patient. Pieces of organs were fixed and stained according to the standard protocol...

Mosquito-borne viral infections are on the rise worldwide and can lead to severe symptoms such as haemorrhage, encephalitis, arthritis or microcephaly. A protective immune response following mosquito-borne viral infections requires the generation of a controlled and balanced immune response leading to viral clearance without immunopathology. Here, regulatory T cells play a central role in restoring immune homeostasis. In current review, we aim to provide an overview and summary of the phenotypes of FOXP3+ Tregs in various mosquito-borne arboviral disease, their association with disease severity and their functional characteristics...

Respiratory viral infections, including human metapneumovirus (HMPV), remain a leading cause of morbidity and mortality in neonates and infants. However, the mechanisms behind the increased sensitivity to those respiratory viral infections in neonates are poorly understood. Neonates, unlike adults, have several anti-inflammatory mechanisms in the lung, including elevated baseline expression of PD-L1, a ligand for the inhibitory receptor PD-1. We thus hypothesized that neonates would rely on PD-1:PD-L1 signaling to restrain antiviral CD8 responses...

Avian influenza viruses (AIV) of the H7N7 subtype are enzootic in the wild bird reservoir in Europe, cause infections in poultry, and have sporadically infected humans. The non-structural protein PB1-F2 is encoded in a second open frame in the polymerase segment PB1 and its sequence varies with the host of origin. While mammalian isolates predominantly carry truncated forms, avian isolates typically express full-length PB1-F2. PB1-F2 is a virulence factor of influenza viruses in mammals. It modulates the host immune response, causing immunopathology and increases pro-inflammatory responses...

Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease that is characterized by mucocutaneous blister formation resulting in painful erosions. The autoantibody immunoglobulin (Ig) G directed toward glycoproteins desmoglein (Dsg) 3 and desmoglein 1 is the main underlying mechanism behind PV leading to intraepithelial clefting and bulla formation. Patients usually present with oral ulcers causing severe pain and dysphagia that can be misdiagnosed as erythema multiforme (EM) or viral infections. The diagnostic process requires the correlation between clinical, histopathological, and immunopathological findings...

The COVID-19 pandemic had a significant economic and health impact worldwide. It also reinforced the misperception that only viruses can pose a threat to human existence, overlooking that bacteria (e.g., plague and cholera) have severely haunted and shaped the course of human civilization. While the world is preparing for the next viral pandemic, it is again overlooking a silent one: antimicrobial resistance (AMR). This review proposes to show the impact of bacterial infections on civilization to remind the pandemic potential...

Passive immunotherapies have been used to treat severe respiratory infections for over a century, with convalescent blood products from recovered individuals given to patients with influenza-related pneumonia as long ago as the Spanish flu pandemic. However, passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (hIVIG) has not provided unequivocal evidence of a clinical benefit for severe respiratory infections including influenza and COVID-19. Efficacy trials, primarily conducted in late-stage disease, have demonstrated inconsistent efficacy and clinical benefit for hIVIG treatment of severe respiratory infections...

BACKGROUND: Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic, 16 amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter, linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6 amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy...

Preventative anti-cancer vaccination strategies have long been hampered by the challenge of targeting the diverse array of potential tumor antigens, with successes to date limited to cancers with viral etiologies. Identification and vaccination against frameshift neoantigens conserved across multiple species and tumor histologies is a potential cancer preventative strategy currently being investigated. Companion dogs spontaneously develop cancers at a similar incidence to those in people and are a complementary comparative patient population for the development of novel anti-cancer therapeutics...

Dengue disease is characterized by an inflammatory-mediated immunopathology, with elevated levels of circulating factors including TNF-α and IL-6. If the damaging inflammatory pathways could be blocked without loss of antiviral responses or exacerbating viral replication, then this would be of potential therapeutic benefit. The study here has investigated the Vav guanine exchange factors as a potential alternative signaling pathway that may drive dengue virus (DENV)-induced inflammatory responses, with a focus on Vav1 and 2...

This review gives an overview of the protective role of CD8+ T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8+ T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8+ T cells in the upper and lower airway during infection is discussed, and CD8+ T-cell responses following vaccination, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explained the correlation between CD8+ T cells and COVID-19 severity...

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field of study within the scientific community. HSV, renowned for its latent infection capability, gives rise to a spectrum of neurological expressions, ranging from mild symptoms to severe encephalitis. The enigmatic interplay between the virus and the host's immune responses profoundly shapes the outcome of these infections. This review delves into the multifaceted immune reactions triggered by HSV within neural tissues, intricately encompassing the interplay between innate and adaptive immunity...

Multiple sclerosis is the most common demyelinating disease that develops in genetically predisposed individuals through various immunopathological mechanisms induced by environmental factors, especially viral infections. Th1, Th17, γδ T cells, activated macrophages, MAIT cells, and proinflammatory cytokines, particularly IFN-γ, TNF, IL-17, and GM-CSF, are the principal pathological players whose activities cause damage to the white matter. Furthermore, a recently identified subset of CD4+ T cells has been found to migrate directly to the brain cortex and cause damage to neurons...

CD4+ T cells play an important role in immune responses against pathogens and cancer cells. Although their main task is to provide help to other effector immune cells, a growing number of infections and cancer entities have been described in which CD4+ T cells exhibit direct effector functions against infected or transformed cells. The most important cell type in this context are cytotoxic CD4+ T cells (CD4+ CTL). In infectious diseases anti-viral CD4+ CTL are mainly found in chronic viral infections. Here, they often compensate for incomplete or exhausted CD8+ CTL responses...

BACKGROUND: A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data. METHODS: Our study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV)...

BACKGROUND: Hendra virus is an emerging virus with a geographically broad host reservoir. In humans, Hendra virus causes excessive inflammatory disease of the lung and nervous system. Our current understanding as to how Hendra virus or what factors induce inflammation is limited and as such, there are currently no therapeutic options available for patients who contract Hendra virus. Recent studies have identified viral aggregating proteins as drivers of inflammation in influenza A virus and SARS-CoV-2 virus...