The interactions between PML nuclear bodies and small and medium size DNA viruses

Abstract

Promyelocytic leukemia nuclear bodies (PM NBs), often referred to as membraneless organelles, are dynamic macromolecular protein complexes composed of a PML protein core and other transient or permanent components. PML NBs have been shown to play a role in a wide variety of cellular processes. This review describes in detail the diverse and complex interactions between small and medium size DNA viruses and PML NBs that have been described to date. The PML NB components that interact with small and medium size DNA viruses include PML protein isoforms, ATRX/Daxx, Sp100, Sp110, HP1, and p53, among others. Interaction between viruses and components of these NBs can result in different outcomes, such as influencing viral genome expression and/or replication or impacting IFN-mediated or apoptotic cell responses to viral infection. We discuss how PML NB components abrogate the ability of adenoviruses or Hepatitis B virus to transcribe and/or replicate their genomes and how papillomaviruses use PML NBs and their components to promote their propagation. Interactions between polyomaviruses and PML NBs that are poorly understood but nevertheless suggest that the NBs can serve as scaffolds for viral replication or assembly are also presented. Furthermore, complex interactions between the HBx protein of hepadnaviruses and several PML NBs-associated proteins are also described. Finally, current but scarce information regarding the interactions of VP3/apoptin of the avian anellovirus with PML NBs is provided. Despite the considerable number of studies that have investigated the functions of the PML NBs in the context of viral infection, gaps in our understanding of the fine interactions between viruses and the very dynamic PML NBs remain. The complexity of the bodies is undoubtedly a great challenge that needs to be further addressed.

Epigenetic Restriction Factors (eRFs) in Virus Infection

“…They are also referred to as the nuclear domains 10 (ND10) based on their average number of 10 loci per nucleus in various cultured cells [ 20 ]. They are a multiprotein complex consisting of a diverse and dynamic array of both positive and negative transcription regulators known to be involved in many key cellular processes, including DNA damage response, apoptosis, autophagy, cellular differentiation, oncogenesis, epigenetic silencing, and antiviral defenses [ 18 , 19 , 21 , 22 , 23 ]. In addition to the PML-NBs’ permanent members, like PML (TRIM19), Sp100, and DAXX, various other proteins transiently reside in the PML-NBs based on cell stage, type, and condition.…”

“…It also recruits epigenetic modifiers such as HP1 and the histone methyltransferase EZH2 which is responsible for the deposition of H3K27me3 marks [ 25 ]. As many as 271 proteins have been reported to be associated with PML-NB under various conditions [ 22 ]. Many of these proteins have been recognized as intrinsic eRFs in diverse virus systems, but because they all colocalize with the PML-NBs, we will collectively consider them as part of the same macromolecular ND-10 complex.…”

“…In adenoviruses (AdVs), it has been reported that DAXX changes the epigenetic status of viral promoters in cooperation with ATRX by repositioning H3.3 variants [ 39 ]. Also, Sp100A, a PML-NB protein, recruits the heterochromatin protein 1 alpha (HP1α) to condense viral DNA, leading to transcriptional repression of the AdV genome [ 22 ]. FOXO4, a PML-NB-associated transcription factor, was found to promote heterochromatinization and silencing of hepatitis B virus (HBV) DNA [ 40 ].…”

The mysterious anelloviruses: investigating its role in human diseases

“…Scientific findings show that high viral loads can be involved in the initiation or progression of human cancers [ 10 , 90 ]. Unlike viruses such as adenoviruses, which have the ability to induce the S phase of the host cell cycle to aid in the replication of their genomes, anelloviruses do not, but can replicate rapidly in their host cells [ 91 ]. Also, based on experimental findings, the presence of AVs can highlight the process of inducing cell proliferation or oncogenic space created by oncogenic viruses.…”

PML Nuclear bodies: the cancer connection and beyond

“…In this review, we focus on PML bodies as important organelles in the complex system of the cell. The links between PML bodies and viruses are not detailed here as recent reviews have explored this active research field [ 6 , 7 ]. PML bodies have been extensively investigated in cancer research, especially acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL).…”