Human Herpesvirus 6A Induces Dendritic Cell Death and HMGB1 Release without Virus Replication

Gustafsson, Rasmus

doi:10.3390/pathogens10010057

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…[ 27 ] The HMGB1 release was driven by the human herpesvirus 6A. [ 28 ] Importantly, the HMGB1 level was elevated in the serum of EV71‐induced HFMD patients and was aggravated in severe and critical HFMD patients. [ 12 ] Consistent with our previous study, the present study also found that the HMGB1 expression was increased in the serum of HFMD patients and EV71‐infected RD cells in a time‐ and MOI‐dependent manner.…”

Section: Discussionmentioning

confidence: 99%

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF‐κB/NLRP3 axis

Zhang,

Li,

Deng

et al. 2024

J Biochem & Molecular Tox

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Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. Nowadays, there are still no effective antiviral drugs for EV71 infection. High mobility group box 1 (HMGB1) is reported to be highly expressed in HFMD patients. However, the role and underlying mechanism of HMGB1 in EV71‐associated HFMD are still unclear. HMGB1 expression was detected using RT‐qPCR and western blot assays. Loss‐ and gain‐function experiments were performed to evaluate the effects of HMGB1 on EV71‐infected cells. The virus titer was examined by TCID50. CCK‐8 and flow cytometry assays were applied to detect the cell viability and cell cycle. Oxidative stress was determined by relative commercial kits. HMGB1 level was elevated in the serum of EV71‐infected patients with HFMD and EV71‐induced RD cells. EV71 infection induced the transfer of HMGB1 from the nucleus into the cytoplasm. HMGB1 knockdown inhibited virus replication, viral protein (VP1) expression and promoted antiviral factor expression. In addition, the inhibition of HMGB1 improved cell viability, protected against S phase arrest, and inhibited EV71‐induced cell injury and oxidative stress, whereas HMGB1 overexpression showed the opposite effects. In terms of mechanism, HMGB1 overexpression activated the TLR4/NF‐κB/NLRP3 signaling pathway and promoted cell pyroptosis. The inhibition of TLR4 and NF‐κB reversed the effects of HMGB1 overexpression on virus replication, oxidative stress, and pyroptosis. In conclusion, HMGB1 knockdown inhibits EV71 replication and attenuates pyroptosis through TLR4/NF‐κB/NLRP3 axis.

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Section: Discussionmentioning

confidence: 99%

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF‐κB/NLRP3 axis

Zhang,

Li,

Deng

et al. 2024

J Biochem & Molecular Tox

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“…HHV-6 induces syncytia but also gives semi-lytic infection with dying cells and cell debris. DC exposure to HHV-6A result in cell death and release of high mobility group box 1 (HMGB1) protein ( 80 ). This may occur also in the CNS as HHV-6A can induce vigorous apoptosis of a human oligodendrocytes ( 81 ).…”

Section: Hhv-6 In Msmentioning

confidence: 99%

Human Herpesvirus 6A Is a Risk Factor for Multiple Sclerosis

Lundström

Gustafsson

2022

Front. Immunol.

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The role for human herpesvirus (HHV)-6A or HHV-6B in multiple sclerosis (MS) pathogenesis has been controversial. Possibly because the damage of the virus infection may occur before onset of clinical symptoms and because it has been difficult to detect active infection and separate serological responses to HHV-6A or 6B. Recent studies report that in MS patients the serological response against HHV-6A is increased whereas it is decreased against HHV-6B. This effect seems to be even more pronounced in MS patients prior to diagnosis and supports previous studies postulating a predomination for HHV-6A in MS disease and suggests that the infection is important at early stages of the disease. Furthermore, HHV-6A infection interacts with other factors suspected of modulating MS susceptibility and progression such as infection with Epstein-Barr virus (EBV) and Cytomegalovirus (CMV), tobacco smoking, HLA alleles, UV irradiation and vitamin D levels. The multifactorial nature of MS and pathophysiological role for HHV-6A in inflammation and autoimmunity are discussed.

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“…HHV-6A infection of DCs can cause DC cell death [ 145 ]. High mobility group box 1 (HMGB-1) is a protein located in the nucleus that acts as an alarmin and is capable of stimulating the innate immune system through either active release or passive release following cell death [ 146 ].…”

Section: Immune Cell Responsesmentioning

confidence: 99%

“…In addition, infection altered the cytokine profile. While TH1 cytokine expression was unaffected, levels of cytokines produced by TH2 cells were significantly elevated relative to the control [ 145 ].…”

Section: Immune Cell Responsesmentioning

confidence: 99%

Evasion of the Host Immune Response by Betaherpesviruses

Sausen

Reed

Bhutta

et al. 2021

IJMS

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The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. In this review, we will highlight the complex interplay between betaherpesviruses and the human immune response, focusing on protein function. We will explore methods by which the immune system first responds to betaherpesvirus infection as well as mechanisms by which viruses subvert normal cellular functions to evade the immune system and facilitate viral latency, persistence, and reactivation. Lastly, we will briefly discuss recent advances in vaccine technology targeting betaherpesviruses. This review aims to further elucidate the dynamic interactions between betaherpesviruses and the human immune system.

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Human Herpesvirus 6A Induces Dendritic Cell Death and HMGB1 Release without Virus Replication

Cited by 5 publications

References 30 publications

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF‐κB/NLRP3 axis

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF‐κB/NLRP3 axis

Human Herpesvirus 6A Is a Risk Factor for Multiple Sclerosis

Evasion of the Host Immune Response by Betaherpesviruses

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