HHV-6B reduces autophagy and induces ER stress in primary monocytes impairing their survival and differentiation into dendritic cells

Romeo, Maria Anele; Montani, Maria Saveria Gilardini; Falcinelli, Luca; Gaeta, Aurelia; Nazzari, Cristina; Faggioni, Alberto; Cirone, Mara

doi:10.1016/j.virusres.2019.197757

Cited by 13 publications

(12 citation statements)

References 41 publications

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“…However, macroautophagy or the selective forms of autophagy such as xenophagy are often dysregulated by viruses as a smart strategy to prevent them reaching the lysosomes, where they may be eliminated by the lysosomal proteases [ 12 ]. By reducing autophagy, viruses may exacerbate ER stress and this may shift the prosurvival function of UPR into cell death, an effect that can be advantageous for viruses if the infected cells belong to the immune system [ 13 , 14 , 15 , 16 ]. Interestingly, activated ER stress and UPR may contribute to the production of proinflammatory cytokines.…”

Section: Viruses Er Stress Upr Activation and Inflammationmentioning

confidence: 99%

ER Stress, UPR Activation and the Inflammatory Response to Viral Infection

Cirone

2021

Viruses

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The response to invading pathogens such as viruses is orchestrated by pattern recognition receptor (PRR) and unfolded protein response (UPR) signaling, which intersects and converges in the activation of proinflammatory pathways and the release of cytokines and chemokines that harness the immune system in the attempt to clear microbial infection. Despite this protective intent, the inflammatory response, particularly during viral infection, may be too intense or last for too long, whereby it becomes the cause of organ or systemic diseases itself. This suggests that a better understanding of the mechanisms that regulate this complex process is needed in order to achieve better control of the side effects that inflammation may cause while potentiating its protective role. The use of specific inhibitors of the UPR sensors or PRRs or the downstream pathways activated by their signaling could offer the opportunity to reach this goal and improve the outcome of inflammation-based diseases associated with viral infections.

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Section: Viruses Er Stress Upr Activation and Inflammationmentioning

confidence: 99%

ER Stress, UPR Activation and the Inflammatory Response to Viral Infection

Cirone

2021

Viruses

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“…HHV-6A infection of astrocytoma cells and primary neurons reduces autophagy. This leads to the accumulation of misfolded and aggregated proteins, increases the production of A␤, and activates endoplasmic reticulum stress, which in turn promotes both the hyperphosphorylation of tau protein and the unfolded protein response, all phenomena prominent in AD (282,(296)(297)(298).…”

Section: Evidence Linking Vzv With Admentioning

confidence: 99%

“…HHV-6A infection of CNS cells leads to the accumulation of misfolded and aggregated proteins, increases the production of A␤, and promotes both the hyperphosphorylation of tau protein and the unfolded protein response, all phenomena prominent in AD (282,(296)(297)(298). Specific antiviral therapy both reduces viral load in diseased tissue or blood and is followed by clinical improvement.…”

Section: Conclusion: Hhv-6a/b and Admentioning

confidence: 99%

Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation

2020

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SUMMARY Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B), collectively termed HHV-6A/B, are neurotropic viruses that permanently infect most humans from an early age. Although most people infected with these viruses appear to suffer no ill effects, the viruses are a well-established cause of encephalitis in immunocompromised patients. In this review, we summarize the evidence that the viruses may also be one trigger for febrile seizures (including febrile status epilepticus) in immunocompetent infants and children, mesial temporal lobe epilepsy, multiple sclerosis (MS), and, possibly, Alzheimer’s disease. We propose criteria for linking ubiquitous infectious agents capable of producing lifelong infection to any neurologic disease, and then we examine to what extent these criteria have been met for these viruses and these diseases.

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“…To the best of our knowledge, no other viruses are recognized to modulate cell fate decisions in solid tissues in a way that facilitates persistence. Some herpesviruses impact the choice between progenitor/differentiated cell fates in infected immune cells, for example Epstein-Barr Virus (EBV) restricts B-cell differentiation to facilitate viral latency (Knox and Carrigan, 1992;Niiya et al, 2006;Onnis et al, 2012;Romeo et al, 2019;Styles et al, 2017). Herpesviruses, polyomaviruses, and hepadnaviruses encode proteins proposed to activate YAP1/TAZ or alter Hippo signaling (Hwang et al, 2014;Liu et al, 2014Nguyen et al, 2014;Shanzer et al, 2015;Tian et al, 2004;.…”

Section: Discussionmentioning

confidence: 99%

YAP1 Activation by Human Papillomavirus E7 Promotes Basal Cell Identity in Squamous Epithelia

Hatterschide

Castagnino

Kim

et al. 2021

Preprint

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Persistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly five percent of cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative cancers at the same anatomical site, prompting the hypothesis that an HPV-encoded protein inactivates the Hippo pathway and activates the Hippo effector YAP1. The HPV E7 oncoprotein is required for HPV infection and for HPV-mediated oncogenic transformation. We investigated the effects of HPV oncoproteins on YAP1 and found that E7 activates YAP1, promoting YAP1 nuclear localization in basal epithelial cells. YAP1 activation by HPV E7 required that E7 bind and degrade the tumor suppressor PTPN14. E7 required YAP1 transcriptional activity to extend the lifespan of primary keratinocytes, indicating that YAP1 activation contributes to E7 carcinogenic activity. Maintaining infection in basal cells is critical for HPV persistence, and here we demonstrate that YAP1 activation causes HPV E7 expressing cells to be retained in the basal compartment of stratified epithelia. We propose that YAP1 activation resulting from PTPN14 inactivation is an essential, targetable activity of the HPV E7 oncoprotein relevant to HPV infection and carcinogenesis.

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HHV-6B reduces autophagy and induces ER stress in primary monocytes impairing their survival and differentiation into dendritic cells

Cited by 13 publications

References 41 publications

ER Stress, UPR Activation and the Inflammatory Response to Viral Infection

ER Stress, UPR Activation and the Inflammatory Response to Viral Infection

Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation

YAP1 Activation by Human Papillomavirus E7 Promotes Basal Cell Identity in Squamous Epithelia

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