Interleukin 1β triggers synaptic and memory deficits in Herpes simplex virus type-1-infected mice by downregulating the expression of synaptic plasticity-related genes via the epigenetic MeCP2/HDAC4 complex.

Extensive research provides evidence that neuroinflammation underlies numerous brain disorders. However, the molecular mechanisms by which inflammatory mediators determine synaptic and cognitive dysfunction occurring in neurodegenerative diseases (e.g.

Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents.

Resveratrol (RSV) is a natural stilbene polyphenolic compound found in several plant species. It is characterized by antioxidant properties, and its role in controlling viral replication has been demonstrated for different viral infections. Despite its promising antiviral properties, RSV biological activity is limited by its low bioavailability and high metabolic rate.

The Inhibition of DNA Viruses by the Amphibian Antimicrobial Peptide Temporin G: A Virological Study Addressing HSV-1 and JPCyV.

Herpes simplex virus type-1 (HSV-1) and John Cunningham polyomavirus (JCPyV) are widely distributed DNA viruses causing mainly asymptomatic infection, but also mild to very severe diseases, especially when these viruses reach the brain. Some drugs have been developed to inhibit HSV-1 replication in host cells, but their prolonged use may induce resistance phenomena. In contrast, to date, there is no cure for JCPyV.

Role of HSV-1 in Alzheimer's disease pathogenesis: A challenge for novel preventive/therapeutic strategies.

Herpes simplex virus-1 (HSV-1) is a ubiquitous DNA virus able to establish a life-long latent infection in host sensory ganglia. Following periodic reactivations, the neovirions usually target the site of primary infection causing recurrent diseases in susceptible individuals. However, reactivated HSV-1 may also reach the brain resulting in severe herpetic encephalitis or in asymptomatic infections.

Influenza Virus Down-Modulates G6PD Expression and Activity to Induce Oxidative Stress and Promote Its Replication.

Influenza virus infection induces oxidative stress in host cells by decreasing the intracellular content of glutathione (GSH) and increasing reactive oxygen species (ROS) level. Glucose-6-phosphate dehydrogenase (G6PD) is responsible for the production of reducing equivalents of nicotinamide adenine dinucleotide phosphate (NADPH) that is used to regenerate the reduced form of GSH, thus restoring redox homeostasis. Cells deficient in G6PD display elevated levels of ROS and an increased susceptibility to viral infection, although the consequences of G6PD modulation during viral infection remain to be elucidated.

Recurrent Herpes Simplex Virus Type 1 (HSV-1) Infection Modulates Neuronal Aging Marks in In Vitro and In Vivo Models.

Herpes simplex virus 1 (HSV-1) is a widespread neurotropic virus establishing a life-long latent infection in neurons with periodic reactivations. Recent studies linked HSV-1 to neurodegenerative processes related to age-related disorders such as Alzheimer's disease. Here, we explored whether recurrent HSV-1 infection might accelerate aging in neurons, focusing on peculiar marks of aged cells, such as the increase in histone H4 lysine (K) 16 acetylation (ac) (H4K16ac); the decrease of H3K56ac, and the modified expression of Sin3/HDAC1 and HIRA proteins.

SARS-CoV-2: Comparative analysis of different RNA extraction methods.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the COVID-19 pandemic. Although other diagnostic methods have been introduced, detection of viral genes on oro- and nasopharyngeal swabs by reverse-transcription real time-PCR (rRT-PCR) assays is still the gold standard. Efficient viral RNA extraction is a prerequisite for downstream performance of rRT-PCR assays.

Ca -dependent release of ATP from astrocytes affects herpes simplex virus type 1 infection of neurons.

Astrocytes provide metabolic support for neurons and modulate their functions by releasing a plethora of neuroactive molecules diffusing to neighboring cells. Here we report that astrocytes also play a role in cortical neurons' vulnerability to Herpes simplex virus type-1 (HSV-1) infection through the release of extracellular ATP. We found that the interaction of HSV-1 with heparan sulfate proteoglycans expressed on the plasma membrane of astrocytes triggered phospholipase C-mediated IP -dependent intracellular Ca transients causing extracellular release of ATP.

Multiple Herpes Simplex Virus-1 (HSV-1) Reactivations Induce Protein Oxidative Damage in Mouse Brain: Novel Mechanisms for Alzheimer's Disease Progression.

Compelling evidence supports the role of oxidative stress in Alzheimer's disease (AD) pathophysiology. Interestingly, Herpes simplex virus-1 (HSV-1), a neurotropic virus that establishes a lifelong latent infection in the trigeminal ganglion followed by periodic reactivations, has been reportedly linked both to AD and to oxidative stress conditions. Herein, we analyzed, through biochemical and redox proteomic approaches, the mouse model of recurrent HSV-1 infection we previously set up, to investigate whether multiple virus reactivations induced oxidative stress in the mouse brain and affected protein function and related intracellular pathways.

The "Three Italy" of the COVID-19 epidemic and the possible involvement of SARS-CoV-2 in triggering complications other than pneumonia.

Coronavirus disease 2019 (COVID-19), first reported in Wuhan, the capital of Hubei, China, has been associated to a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In March 2020, the World Health Organization declared the SARS-CoV-2 infection a global pandemic. Soon after, the number of cases soared dramatically, spreading across China and worldwide.

Experimental Data Based Machine Learning Classification Models with Predictive Ability to Select in Vitro Active Antiviral and Non-Toxic Essential Oils.

In the last decade essential oils have attracted scientists with a constant increase rate of more than 7% as witnessed by almost 5000 articles. Among the prominent studies essential oils are investigated as antibacterial agents alone or in combination with known drugs. Minor studies involved essential oil inspection as potential anticancer and antiviral natural remedies.

Herpes Simplex Virus-1 in the Brain: The Dark Side of a Sneaky Infection.

Herpes simplex virus-1 (HSV-1) establishes latency preferentially in sensory neurons of peripheral ganglia. A variety of stresses can induce recurrent reactivations of the virus, which spreads and then actively replicates to the site of primary infection (usually the lips or eyes). Viral particles produced following reactivation can also reach the brain, causing a rare but severe form of diffuse acute infection, namely herpes simplex encephalitis.

Herpes Simplex Virus Type-1 Infection Impairs Adult Hippocampal Neurogenesis via Amyloid-β Protein Accumulation.

We previously reported that Herpes simplex virus type-1 (HSV-1) infection of cultured neurons triggered intracellular accumulation of amyloid-β protein (Aβ) markedly impinging on neuronal functions. Here, we demonstrated that HSV-1 affects in vitro and in vivo adult hippocampal neurogenesis by reducing neural stem/progenitor cell (NSC) proliferation and their neuronal differentiation via intracellular Aβ accumulation. Specifically, cultured NSCs were more permissive for HSV-1 replication than mature neurons and, once infected, they exhibited reduced proliferation (assessed by 5'-bromo-deoxyuridine incorporation, Ki67 immunoreactivity, and Sox2 mRNA expression) and impaired neuronal differentiation in favor of glial phenotype (evaluated by immunoreactivity for the neuronal marker MAP2, the glial marker glial fibrillary astrocyte protein, and the expression of the proneuronal genes Mash1 and NeuroD1).

Corrigendum: GSH-C4 Acts as Anti-inflammatory Drug in Different Models of Canonical and Cell Autonomous Inflammation Through NFκB Inhibition.

[This corrects the article DOI: 10.3389/fimmu.2019.

Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice.

Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation.

GSH-C4 Acts as Anti-inflammatory Drug in Different Models of Canonical and Cell Autonomous Inflammation Through NFκB Inhibition.

An imbalance in GSH/GSSG ratio represents a triggering event in pro-inflammatory cytokine production and inflammatory response. However, the molecular mechanism(s) through which GSH regulates macrophage and cell autonomous inflammation remains not deeply understood. Here, we investigated the effects of a derivative of GSH, the N-butanoyl glutathione (GSH-C4), a cell permeable compound, on lipopolisaccharide (LPS)-stimulated murine RAW 264.

A Novel Method to Titrate Herpes Simplex Virus-1 (HSV-1) Using Laser-Based Scanning of Near-Infrared Fluorophores Conjugated Antibodies.

Among several strategies used for Herpes simplex virus (HSV) detection in biological specimens, standard plaque assay (SPA) remains the most reliable method to evaluate virus infectivity and quantify viral replication. However, it is a manual procedure, thereby affected by operator subjectivity, and it may be particularly laborious for multiple sample analysis. Here we describe an innovative method to perform the titration of HSV type 1 (HSV-1) in different samples, using the "In-Cell Western" Assay (ICW) from LI-COR, a quantitative immunofluorescence assay that exploits laser-based scanning of near infrared (NIR).

Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons.

Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs.

Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-β protein accumulation.

Increasing evidence suggests that recurrent Herpes Simplex Virus type 1 (HSV-1) infection spreading to the CNS is a risk factor for Alzheimer's Disease (AD) but the underlying mechanisms have not been fully elucidated yet. Here we demonstrate that in cultured mouse cortical neurons HSV-1 induced Ca(2+)-dependent activation of glycogen synthase kinase (GSK)-3. This event was critical for the HSV-1-dependent phosphorylation of amyloid precursor protein (APP) at Thr668 and the following intraneuronal accumulation of amyloid-β protein (Aβ).

Herpes simplex virus type 1 infection in neurons leads to production and nuclear localization of APP intracellular domain (AICD): implications for Alzheimer's disease pathogenesis.

Several data indicate that neuronal infection with herpes simplex virus type 1 (HSV-1) causes biochemical alterations reminiscent of Alzheimer's disease (AD) phenotype. They include accumulation of amyloid-β (Aβ), which originates from the cleavage of amyloid precursor protein (APP), and hyperphosphorylation of tau protein, which leads to neurofibrillary tangle deposition. HSV-1 infection triggers APP processing and drives the production of several fragments including APP intracellular domain (AICD) that exerts transactivating properties.

HSV-1 and Alzheimer's disease: more than a hypothesis.

Among the multiple factors concurring to Alzheimer's disease (AD) pathogenesis, greater attention should be devoted to the role played by infectious agents. Growing epidemiological and experimental evidence suggests that recurrent herpes simplex virus type-1 (HSV-1) infection is a risk factor for AD although the underlying molecular and functional mechanisms have not been fully elucidated yet. Here, we review literature suggesting the involvement of HSV-1 infection in AD also briefly mentioning possible pharmacological implications of these findings.

Infectious agents and neurodegeneration.

A growing body of epidemiologic and experimental data point to chronic bacterial and viral infections as possible risk factors for neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Infections of the central nervous system, especially those characterized by a chronic progressive course, may produce multiple damage in infected and neighbouring cells. The activation of inflammatory processes and host immune responses cause chronic damage resulting in alterations of neuronal function and viability, but different pathogens can also directly trigger neurotoxic pathways.

Sublethal doses of β-amyloid peptide abrogate DNA-dependent protein kinase activity.

Accumulation of DNA damage and deficiency in DNA repair potentially contribute to the progressive neuronal loss in neurodegenerative disorders, including Alzheimer disease (AD). In multicellular eukaryotes, double strand breaks (DSBs), the most lethal form of DNA damage, are mainly repaired by the nonhomologous end joining pathway, which relies on DNA-PK complex activity. Both the presence of DSBs and a decreased end joining activity have been reported in AD brains, but the molecular player causing DNA repair dysfunction is still undetermined.