Neuropathogenic and non-neuropathogenic EHV-1 strains induce the accumulation of hyperphosphorylated Tau in primary murine neurons

Cymerys, Joanna; Słońska, Anna; Chodkowski, Marcin; Golke, Anna; Krzyżowska, Małgorzata; Banbura, M.

doi:10.4149/av_2020_407

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…However, the mechanisms of the neuronal damage of EHV‐1 are still mysterious. Therefore, a study (Cymerys et al, 2020) was carried out to define the phosphorylation status of tau protein in neuronal cell culture infected with EHV‐1. The authors illustrated for the first time that EHV‐1 infection causes accumulation of hyperphosphorylated tau in primary murine neurons.…”

Section: The Equine Herpesvirus Type‐1 (Ehv‐1)mentioning

confidence: 99%

Review of two viral agents of economic importance to the equine industry (equine herpesvirus‐1, and equine arteritis virus)

Mahmoud

Fouad

Amin

2022

Equine Veterinary Education

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Equine herpesvirus type-1 (EHV-1) and equine arteritis virus (EAV) are infectious agents that cause serious health risks to horse populations and are disbursed worldwide, which can lead to significant financial losses. In addition to being responsible for abortion and neonatal death, these viruses are associated with respiratory illness. Although previous research and reviews have been written on these viruses, both viruses still affect horse populations around the world and the vaccines currently available are not completely protective, especially against EHV-1 and equine herpes myeloencephalopathy (EHM).Moreover, EAV is considered a threat to the $102 billion equine industry in the United States. As a result, these viruses represent a huge threat to the horse industry and efforts geared towards preventing the outbreak of the disease are strongly encouraged.For this reason, updates about these viruses are necessary and require more and more discussion on the nature and characteristics of these viruses to know how to overcome them. Prevention and control of abortion and neonatal foal death caused by each of the two viruses depend on appropriate management strategies coupled with prophylactic vaccination. This review presents the latest detailed information on EHV-1 and EAV from several aspects such as transmission, clinical signs, pathogenesis, latest developments on the treatment of the diseases, vaccination, and finally challenges and future perspectives. The information presented herein will be useful in understanding EHV-1 and EAV and formulating policies that can help to limit the spread of these viruses within horse populations.

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Section: The Equine Herpesvirus Type‐1 (Ehv‐1)mentioning

confidence: 99%

Review of two viral agents of economic importance to the equine industry (equine herpesvirus‐1, and equine arteritis virus)

Mahmoud

Fouad

Amin

2022

Equine Veterinary Education

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HSV-1 infection induces phosphorylated tau propagation among neurons via extracellular vesicles

Protto,

Miteva,

Iannuzzi

et al. 2024

mBio

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Extracellular vesicles (EV), key players in cell-to-cell communication, may contribute to disease propagation in several neurodegenerative diseases, including Alzheimer’s disease (AD), by favoring the dissemination of neurotoxic proteins within the brain. Interestingly, growing evidence supports the role of herpes simplex virus type 1 (HSV-1) infection in the pathogenesis of AD. Here, we investigated whether HSV-1 infection could promote the spread of phosphorylated tau (ptau) among neurons via EV. We analyzed the ptau species that were secreted via EV following HSV-1 infection in neuroblastoma cells and primary neurons, focusing particularly on T205, T181, and T217, the phosphorylation sites mainly associated with AD. Moreover, by overexpressing human tau tagged with GFP (htau GFP ), we found that recipient tau knockout (KO) neurons uptook EV that are loaded with HSV-1-induced phtau GFP . Finally, we exploited an in vivo model of acute infection and assessed that cerebral HSV-1 infection promotes the release of ptau via EV in the brain of infected mice. Overall, our data suggest that, following HSV-1 infection, EV play a role in tau spreading within the brain, thus contributing to neurodegeneration. IMPORTANCE Herpes simplex virus type 1 (HSV-1) infection that reaches the brain has been repeatedly linked with the appearance of the pathognomonic markers of Alzheimer’s disease (AD), including accumulation of amyloid beta and hyperphosphorylated tau proteins, and cognitive deficits. AD is a multifactorial neurodegenerative disease representing the most common form of dementia in the elderly, and no cure is currently available, thus prompting additional investigation on potential risk factors and pathological mechanisms. Here, we demonstrate that the virus exploits the extracellular vesicles (EV) to disseminate phosphorylated tau (ptau) among brain cells. Importantly, we provide evidence that the HSV-1-induced EV-bearing ptau can be undertaken by recipient neurons, thus likely contributing to misfolding and aggregation of native tau, as reported for other AD models. Hence, our data highlight a novel mechanism exploited by HSV-1 to propagate tau-related damage in the brain.

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Equid Alphaherpesvirus 1 (EHV-1) Influences Morphology and Function of Neuronal Mitochondria In Vitro

et al. 2022

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Mitochondria are key cellular organelles responsible for many essential functions, including ATP production, ion homeostasis and apoptosis induction. Recent studies indicate their significant role during viral infection. In the present study, we examined the effects of equine herpesvirus type 1 (EHV-1) infection on the morphology and mitochondrial function in primary murine neurons in vitro. We used three EHV-1 strains: two non-neuropathogenic (Jan-E and Rac-H) and one neuropathogenic (EHV-1 26). The organization of the mitochondrial network during EHV-1 infection was assessed by immunofluorescence. To access mitochondrial function, we analyzed reactive oxygen species (ROS) production, mitophagy, mitochondrial inner-membrane potential, mitochondrial mass, and mitochondrial genes’ expression. Changes in mitochondria morphology during infection suggested importance of their perinuclear localization for EHV-1 replication. Despite these changes, mitochondrial functions were preserved. For all tested EHV-1 strains, the similarities in the increased fold expression were detected only for COX18, Sod2, and Tspo. For non-neuropathogenic strains (Jan-E and Rac-H), we detected mainly changes in the expression of genes related to mitochondrial morphology and transport. The results indicate that mitochondria play an important role during EHV-1 replication in cultured neurons and undergo specific morphological and functional modifications.

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Neuropathogenic and non-neuropathogenic EHV-1 strains induce the accumulation of hyperphosphorylated Tau in primary murine neurons

Cited by 3 publications

References 15 publications

Review of two viral agents of economic importance to the equine industry (equine herpesvirus‐1, and equine arteritis virus)

Review of two viral agents of economic importance to the equine industry (equine herpesvirus‐1, and equine arteritis virus)

HSV-1 infection induces phosphorylated tau propagation among neurons via extracellular vesicles

Equid Alphaherpesvirus 1 (EHV-1) Influences Morphology and Function of Neuronal Mitochondria In Vitro

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