scholarly journals Inflammasome, the Constitutive Heterochromatin Machinery, and Replication of an Oncogenic Herpesvirus

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 846
Author(s):  
Sumita Bhaduri-McIntosh ◽  
Michael T. McIntosh

The success of long-term host–virus partnerships is predicated on the ability of the host to limit the destructive potential of the virus and the virus’s skill in manipulating its host to persist undetected yet replicate efficiently when needed. By mastering such skills, herpesviruses persist silently in their hosts, though perturbations in this host–virus equilibrium can result in disease. The heterochromatin machinery that tightly regulates endogenous retroviral elements and pericentromeric repeats also silences invading genomes of alpha-, beta-, and gammaherpesviruses. That said, how these viruses disrupt this constitutive heterochromatin machinery to replicate and spread, particularly in response to disparate lytic triggers, is unclear. Here, we review how the cancer-causing gammaherpesvirus Epstein–Barr virus (EBV) uses the inflammasome as a security system to alert itself of threats to its cellular home as well as to flip the virus-encoded lytic switch, allowing it to replicate and escape in response to a variety of lytic triggers. EBV provides the first example of an infectious agent able to actively exploit the inflammasome to spark its replication. Revealing an unexpected link between the inflammasome and the epigenome, this further brings insights into how the heterochromatin machinery uses differential strategies to maintain the integrity of the cellular genome whilst guarding against invading pathogens. These recent insights into EBV biology and host–viral epigenetic regulation ultimately point to the NLRP3 inflammasome as an attractive target to thwart herpesvirus reactivation.

2018 ◽  
Vol 185 (2) ◽  
pp. 377-380 ◽  
Author(s):  
Amie E. Hwang ◽  
Vickie Marshall ◽  
David V. Conti ◽  
Bharat N. Nathwani ◽  
Thomas M. Mack ◽  
...  

2019 ◽  
pp. practneurol-2019-002356 ◽  
Author(s):  
Andrew Lee ◽  
Leslie R Bridges ◽  
Mark Lloyd ◽  
Robert Barker ◽  
Damian R Wren ◽  
...  

The incidence of Epstein–Barr virus (EBV)associated lymphoproliferative disorders has increased with greater use of immunomodulatory therapies. We present a woman who developed subacute cognitive decline and unilateral weakness while taking long-term mycophenolate mofetil for granulomatosis with polyangiitis; her postmortem brain histopathology confirmed an EBV-driven lymphoproliferative disorder. Clinicians must have a high index of suspicion for EBV-driven lymphoma in people taking long-term immunosuppression who develop new neurological problems. We review the role of mycophenolate mofetil in EBV-driven lymphoproliferative disorders, and discuss checking EBV status in all patients starting immunosuppression and in older people already taking immunosuppression.


Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1131-1133 ◽  
Author(s):  
Maurizio Arico ◽  
Shinsaku Imashuku ◽  
Rita Clementi ◽  
Shigeyoshi Hibi ◽  
Tomoko Teramura ◽  
...  

Abstract The hemophagocytic lymphohistiocytoses (HLH) comprise a heterogeneous group of disorders characterized by dysregulated activation of T cells and macrophages. Although some patients with HLH harbor perforin gene mutations, the cause of the remaining cases is not known. The phenotype of HLH bears a strong resemblance to X-linked lymphoproliferative disease (XLP), an Epstein-Barr virus (EBV)-associated immunodeficiency resulting from defects in SH2D1A, a small SH2 domain-containing protein expressed in T lymphocytes and natural killer cells. Here it is shown that 4 of 25 male patients with HLH who were examined harbored germline SH2D1A mutations. Among these 4 patients, only 2 had family histories consistent with XLP. On the basis of these findings, it is suggested that all male patients with EBV-associated hemophagocytosis be screened for mutations in SH2D1A. Patients identified as having XLP should undergo genetic counseling, and be followed long-term for development of lymphoma and hypogammaglobulinemia.


2000 ◽  
pp. 827-833 ◽  
Author(s):  
Gianpietro Dotti ◽  
Roberto Fiocchi ◽  
Teresio Motta ◽  
Amando Gamba ◽  
Eliana Gotti ◽  
...  

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