Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation

Tiwari, Deeksha; Mittal, Nitish; Jha, Hem Chandra

doi:10.1016/j.crneur.2022.100046

Cited by 14 publications

(10 citation statements)

References 161 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enhanced AURKA activity during this period can control the phosphorylation of cellular proteins, facilitating appropriate cell division [43]. Various cellular tumour suppressors have previously been affected by EBNA1 [7,44]. Regulatory functions of AURKA include phosphorylating these tumour suppressors.…”

Section: Discussionmentioning

confidence: 99%

“…Studies utilizing siRNA knockdown of EBNA1 depict that this protein is necessary for the EBV genome to persist and cause EBV-positive cells to continue proliferating in-vivo and in-vitro [6]. The interaction of cellular oncogenes and EBNA1 may induce G1/S transition and inhibit apoptosis, causing the infected cells to undergo neoplastic transformation [7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interplay of Aurora kinase A functional residues and Epstein-Barr Nuclear Antigen 1 in Epstein-Barr Virus associated Gastric cancer

Varshney,

Singh,

Kandpal

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Epstein-Barr virus (EBV), an oncogenic gamma-herpesvirus, belongs to group 1 carcinogen and is implicated in various cancers, including gastric cancer. Aurora Kinase A is a major mitotic protein kinase that regulates mitotic progression; overexpression and hyperactivation of AURKA commonly promote genomic instability in many tumours. However, the relationship of functional residues of AURKA and EBV in gastric cancer progression remains unknown. Results We reveal that AURKA overexpression and EBV infection induce aneuploidy in gastric epithelial cells. The AURKA (S89) N-terminal residue is critical for the centrosome maturation process in EBV-infected gastric epithelial cells. The kinase domain residues T287 and T288 of AURKA are essential for centrosome maturation and bipolar spindle formation in EBV-infected gastric cancer cells. We also show that AURKA 287/288 dm reduces the transcript expression of cell cycle markers involved in mitotic entry in EBV infection. This mutant also enhanced the protein expression of p53 and Rb, which was reduced in EBV infection and decreased the Survivin expression. Further, EBNA1, the latent gene of EBV, stabilises the AURKA in its wild-type form when it was mutated at the 89th position but unable to stabilise it when mutated at 287/288 position. These mutants also induce mitotic catastrophe by regulating the apoptosis and autophagy pathway in EBV infection. AURKA287/288 dm also promotes autophagosome formation even in EBV infection. Conclusion Thus, this study demonstrates that the AURKA kinase domain is essential for its functioning and progression of oncogenesis of EBV-infected gastric epithelial cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interplay of Aurora kinase A functional residues and Epstein-Barr Nuclear Antigen 1 in Epstein-Barr Virus associated Gastric cancer

Varshney,

Singh,

Kandpal

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…As shown in Figure 1 above, there are several other viruses, including human herpesvirus-6 (HHV-6), -7 (HHV-7) [ 43 , 128 , 129 , 130 , 131 , 132 ], Epstein–Barr virus (EBV) [ 133 , 134 , 135 , 136 , 137 , 138 , 139 ], cytomegalovirus (CMV) [ 33 , 140 , 141 , 142 , 143 ], varicella zoster virus (VZV) [ 144 , 145 , 146 , 147 ], human immunodeficiency virus [ 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 ], hepatitis C virus (HCV) [ 163 ], enterovirus [ 164 , 165 , 166 ], influenza A virus (IAV) [ 167 , 168 , 169 , 170 , 171 ], and measles [ 172 , 173 , 174 , 175 ], which have ...…”

Section: Other Viruses Implicated In Admentioning

confidence: 99%

Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

Rippee-Brooks,

Wu,

Dong

et al. 2024

Pathogens

View full text Add to dashboard Cite

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aβ42 and hyperphosphorylated tau). Controversies and challenges of the virus–AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion.

show abstract

“…An abnormal cell cycle re-entry in glial cells leads to activation and proliferation of these cells, with glial scar formation and production of inflammatory cytokines. 52 However, although several studies have…”

Section: Ebv-mediated Cns Pathologymentioning

confidence: 99%

Treatment Options for Epstein-Barr Virus-Related Disorders of the Central Nervous System

Andersen¹,

Ernberg²,

Hedström³

2023

IDR

View full text Add to dashboard Cite

Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBVrelated CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.

show abstract

Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation

Cited by 14 publications

References 161 publications

Interplay of Aurora kinase A functional residues and Epstein-Barr Nuclear Antigen 1 in Epstein-Barr Virus associated Gastric cancer

Interplay of Aurora kinase A functional residues and Epstein-Barr Nuclear Antigen 1 in Epstein-Barr Virus associated Gastric cancer

Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

Treatment Options for Epstein-Barr Virus-Related Disorders of the Central Nervous System

Contact Info

Product

Resources

About