The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting

Hornig, Julia; Choi, K. Yeon; McGregor, Alistair

doi:10.1016/j.virol.2017.01.023

Cited by 11 publications

(18 citation statements)

References 121 publications

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“…Although various activities have been linked to these restriction factors, they all seem to mediate transcriptional repression of HCMV gene expression in part via chromatin-based mechanisms [134,137,237]. Both IE1 orthologues of animal cytomegaloviruses as well as HCMV IE1 were shown to associate with DAXX [238][239][240]. The sites of interaction in the two proteins have not been mapped, and it remains unclear whether binding is direct.…”

Section: Role In Inhibition Of Intrinsic Immunitymentioning

confidence: 99%

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

Adamson

Nevels

2020

Viruses

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The human cytomegalovirus (HCMV), one of eight human herpesviruses, establishes lifelong latent infections in most people worldwide. Primary or reactivated HCMV infections cause severe disease in immunosuppressed patients and congenital defects in children. There is no vaccine for HCMV, and the currently approved antivirals come with major limitations. Most approved HCMV antivirals target late molecular processes in the viral replication cycle including DNA replication and packaging. “Bright and early” events in HCMV infection have not been exploited for systemic prevention or treatment of disease. Initiation of HCMV replication depends on transcription from the viral major immediate-early (IE) gene. Alternative transcripts produced from this gene give rise to the IE1 and IE2 families of viral proteins, which localize to the host cell nucleus. The IE1 and IE2 proteins are believed to control all subsequent early and late events in HCMV replication, including reactivation from latency, in part by antagonizing intrinsic and innate immune responses. Here we provide an update on the regulation of major IE gene expression and the functions of IE1 and IE2 proteins. We will relate this insight to experimental approaches that target IE gene expression or protein function via molecular gene silencing and editing or small chemical inhibitors.

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Section: Role In Inhibition Of Intrinsic Immunitymentioning

confidence: 99%

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

Adamson

Nevels

2020

Viruses

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“…GPCMV also encodes HCMV homologs of immediate early genes IE1/IE2 [199], pp65 and gB [200,201]; these viral antigens have been suggested as vaccine candidates against congenital CMV infection. As previously mentioned, and similar to RhCMV, GPCMV also encodes homologs to the subunits of the HCMV pentameric complex gH (gp75), gL (gp115), UL128 (gp129), UL130 (gp131), and UL131 (gp133) that are essential for epithelial tropism [202–204].…”

Section: Animal Models and Cmv: Vaccine Implicationsmentioning

confidence: 99%

A fifty-year odyssey: prospects for a cytomegalovirus vaccine in transplant and congenital infection

Diamond

Rosa

Chiuppesi

et al. 2018

Expert Review of Vaccines

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Introduction: It has been almost fifty years since the Towne strain was used by Plotkin and collaborators as the first vaccine candidate for cytomegalovirus (CMV). While that approach showed partial efficacy, there have been a multitude of challenges to improve on the promise of a CMV vaccine. Efforts have been dichotomized into a therapeutic vaccine for patients with CMV-infected allografts, either stem cells or solid organ, and a prophylactic vaccine for congenital infection. Areas Covered: This review will evaluate research prospects for a therapeutic vaccine for transplant recipients that recognizes CMV utilizing primarily T cell responses. Similarly, we will provide an extensive discussion on attempts to develop a vaccine to prevent the manifestations of congenital infection, based on eliciting a humoral anti-CMV protective response. The review will also describe newer developments that have upended the efforts towards such a vaccine through the discovery of a second pathway of CMV infection that utilizes an alternative receptor for entry using a series of antigens that have been determined to be important for prevention of infection. Expert Commentary: There is a concerted effort to unify separate therapeutic and prophylactic vaccine strategies into a single delivery agent that would be effective for both transplant-related and congenital infection.

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“…PML NB size, number, content, and distribution are controlled by many factors, such as type I and II interferons, cellular stress, DNA damage, and viral infections ( 32 – 39 ). PML NBs have been linked to many viral infections, including cytomegalovirus (CMV) ( 40 – 48 ), herpesviruses, adenoviruses, and papovaviruses ( 33 – 35 ), hepatitis delta virus ( 49 – 51 ), and HBV ( 52 – 59 ), and HBV Cp and polymerase have been reported to interact with PML NBs during infection ( 58 , 59 ). We report here that one HAP, Bay 38-7690, not only induces degradation of Cp but also promotes the formation of Cp aggregates associated with PML NBs in HBV-infected cells.…”

Section: Introductionmentioning

confidence: 99%

The Heteroaryldihydropyrimidine Bay 38-7690 Induces Hepatitis B Virus Core Protein Aggregates Associated with Promyelocytic Leukemia Nuclear Bodies in Infected Cells

Huber

Wolf

Liu

et al. 2018

mSphere

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Despite the availability of effective vaccines and treatments, HBV remains a significant global health concern, with more than 240 million individuals chronically infected. Current treatments are highly effective at controlling viral replication and disease progression but rarely cure infections. Therefore, much emphasis is being placed on finding therapeutics with new drug targets, such as viral gene expression, covalently closed circular DNA formation and stability, capsid formation, and host immune modulators, with the ultimate goal of an HBV cure. Understanding the mechanisms by which novel antiviral agents act will be imperative for the development of curative HBV therapies.

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The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting

Cited by 11 publications

References 121 publications

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

A fifty-year odyssey: prospects for a cytomegalovirus vaccine in transplant and congenital infection

The Heteroaryldihydropyrimidine Bay 38-7690 Induces Hepatitis B Virus Core Protein Aggregates Associated with Promyelocytic Leukemia Nuclear Bodies in Infected Cells

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