Impact of HHV-6A and HHV-6B lytic infection on autophagy and endoplasmic reticulum stress

Romeo, Maria Anele; Masuelli, Laura; Gaeta, Aurelia; Nazzari, Cristina; Granato, Marisa; Montani, Maria Saveria Gilardini; Faggioni, Alberto; Cirone, Mara

doi:10.1099/jgv.0.001176

Cited by 26 publications

(20 citation statements)

References 40 publications

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“…ER stress is known to promote autophagy, and although the interplay between them remains still to be fully elucidated, the activation of UPR arms EIF2α and IRE1 have been reported to trigger autophagy [76, 80]. On the other hand, the inhibition of autophagy may exacerbate ER stress [80], altering the activation of UPR arms, leading for example to the up-regulation of the pro-apoptotic molecule C/EBP homologous protein (CHOP). Of note, CHOP can activate Cyclooxigenase (COX)-2 that in turn may promote the release of Prostaglandin (PG) E2, a DAMP that induces immune suppression [81, 82].…”

Section: Introductionmentioning

confidence: 99%

Autophagy manipulation as a strategy for efficient anticancer therapies: possible consequences

Cirone

Montani

Granato

et al. 2019

J Exp Clin Cancer Res

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Autophagy is a catabolic process whose activation may help cancer cells to adapt to cellular stress although, in some instances, it can induce cell death. Autophagy stimulation or inhibition has been considered an opportunity to treat cancer, especially in combination with anticancer therapies, although autophagy manipulation may be viewed as controversial. Thus, whether to induce or to inhibit autophagy may be the best option in the different cancer patients is still matter of debate. Her we will recapitulate the possible advantages or disadvantages of manipulating autophagy in cancer, not only with the aim to obtain cancer cell death and disable oncogenes, but also to evaluate its interplay with the immune response which is fundamental for the success of anticancer therapies.

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Section: Introductionmentioning

confidence: 99%

Autophagy manipulation as a strategy for efficient anticancer therapies: possible consequences

Cirone

Montani

Granato

et al. 2019

J Exp Clin Cancer Res

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“…HSV‐1 infection and oxidative stress also impair lysosomal function, which is known to occur early in the development of AD . A recent study showed HHV‐6A and HHV‐6B lytic infection also inhibits autophagy and increases endoplasmic reticulum stress, which likely share the same mechanism seen in HSV‐1 infection. Impaired autophagy was found in the AD brain, not in normal brains .…”

Section: Oxidative Stress Induced By Herpesviruses May Contribute To Admentioning

confidence: 96%

Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment

Qin

2019

Journal of Medical Virology

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Accumulating evidence suggests that infections by herpesviruses might be closely linked to Alzheimer's disease (AD). Pathological hallmarks of AD brains include senile plaques induced by amyloid β peptide (Aβ) in the extracellular space and intracellular neurofibrillary tangles (NFTs) consisting of phosphorylated tau protein. The prevailing hypothesis for the mechanism of AD is amyloid cascade reaction. Recent studies revealed that infections by herpesviruses induce the similar pathological hallmarks of AD, including Aβ production, phosphorylation of tau (P-tau), oxidative stress, neuroinflammation, etc. Aβ peptide is regarded as one of the antimicrobial peptides, which inhibits HSV-1 replication. In the elderly, reactivation of herpesviruses might act as an initiator for amyloid cascade reaction in vulnerable individuals, triggering the neurofibrillary formation of phosphorylated tau and inducing oxidative stress and neuroinflammation, which can further contribute to the accumulation of Aβ and P-tau by impairing mitochondria and autophagosome. Epidemiological studies have shown AD susceptibility genes, such as APOE-ε4 allele, are highly linked to infections by herpesviruses. Interestingly, anti-herpesviral therapy significantly reduced the risk of AD in a large population study. Given that herpesviruses are arguably the most prevalent opportunistic pathogens and often reactivate in the elderly, it is reasonable to argue reactivation of herpesviruses might be major culprits for initiating AD in individuals carrying AD susceptibility genes. In this review, we summarize epidemiological and molecular evidence that support for a hypothesis of herpesviral infections and antimicrobial protection in the development of AD, and discuss the implications for future prevention and treatment of the disease.

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“…For the best-studied case of an amyloid-virus interaction, the association between Aβ and herpesvirus infection, it has been proposed that the dysregulation of autophagy might play an essential role. Herpesviruses interfere with autophagy pathways to optimize their replication and to counteract immune response during primary infection, but also during reactivation from latency [112][113][114][115][116][117]. For example, gamma herpesviruses block the final steps of autophagy during the lytic cycle for transportation to the membrane [118,119].…”

Section: Viral Infections Can Indirectly Promote Spontaneous Amyloid mentioning

confidence: 99%

“…For example, gamma herpesviruses block the final steps of autophagy during the lytic cycle for transportation to the membrane [118,119]. Both HSV-1 and HHV-6B are able to block autophagy in infected neurons and peripheral blood cells, respectively [116,117,120]. Remarkably, two other herpesviruses, varicella-zoster virus and HHV-6A, have the opposite effect and promote autophagy to prolong the survival of infected cells [117,121,122].…”

Section: Viral Infections Can Indirectly Promote Spontaneous Amyloid mentioning

confidence: 99%

“…Both HSV-1 and HHV-6B are able to block autophagy in infected neurons and peripheral blood cells, respectively [116,117,120]. Remarkably, two other herpesviruses, varicella-zoster virus and HHV-6A, have the opposite effect and promote autophagy to prolong the survival of infected cells [117,121,122]. It is well established that cells strongly depend on protein quality control systems to maintain homeostasis.…”

Section: Viral Infections Can Indirectly Promote Spontaneous Amyloid mentioning

confidence: 99%

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Mechanisms and therapeutic potential of interactions between human amyloids and viruses

Michiels

Rousseau

Schymkowitz

2020

Cell. Mol. Life Sci.

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The aggregation of specific proteins and their amyloid deposition in affected tissue in disease has been studied for decades assuming a sole pathogenic role of amyloids. It is now clear that amyloids can also encode important cellular functions, one of which involves the interaction potential of amyloids with microbial pathogens, including viruses. Human expressed amyloids have been shown to act both as innate restriction molecules against viruses as well as promoting agents for viral infectivity. The underlying molecular driving forces of such amyloid–virus interactions are not completely understood. Starting from the well-described molecular mechanisms underlying amyloid formation, we here summarize three non-mutually exclusive hypotheses that have been proposed to drive amyloid–virus interactions. Viruses can indirectly drive amyloid depositions by affecting upstream molecular pathways or induce amyloid formation by a direct interaction with the viral surface or specific viral proteins. Finally, we highlight the potential of therapeutic interventions using the sequence specificity of amyloid interactions to drive viral interference.

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Impact of HHV-6A and HHV-6B lytic infection on autophagy and endoplasmic reticulum stress

Cited by 26 publications

References 40 publications

Autophagy manipulation as a strategy for efficient anticancer therapies: possible consequences

Autophagy manipulation as a strategy for efficient anticancer therapies: possible consequences

Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment

Mechanisms and therapeutic potential of interactions between human amyloids and viruses

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