Skip to Main Content
Text size: SmallMediumLargeExtra-Large

Epigenomics of Viral Associated Oral Diseases

AIDS and Immunosuppression Program
Integrative Biology and Infectious Diseases Branch
Division of Extramural Research
 

OBJECTIVE

To support novel research projects that will advance our understanding of the epigenetic basis of viral associated oral diseases to guide the discovery and application of novel epigenomic-based clinical interventions.  Research projects under this initiative will address the following specific objectives:

  • To delineate epigenetic modifications and their potential interactions in cells, tissues and viral components that define the onset and progression of oral diseases.
  • To define the mechanisms of epigenomic deregulation of immune responses against oral viruses, or chromatin exchange in oral immune-mediated anti-viral host responses.
  • To characterize epigenomic deregulation of host’s biological processes that lead to oral lesions and diseases.
  • To define the mechanisms by which changes in host and viral gene expression through functionally relevant epigenomic modifications attenuate or inhibit oral viral pathogenicity and decrease infection. For this studies must:

    --Establish the epigenetic modifications that occur in viral genomes and in each naïve state in oral cells and tissues, and define epigenomic mechanisms by which the host and viral genes are altered in an interacting environment that leads to changes in gene expression

    --Define mechanisms and experimental approaches to modify epigenetic changes to attenuate or inhibit oral viral pathogenicity

  • To define the mechanisms by which drugs and therapies affect host and viral epigenomic modifications. 

The goal is to correlate modifications in the host and viral epigenomes with pathophysiological changes in oral cells and tissues that lead to oral diseases.  For this, genome-wide, biochemical, and molecular epigenetic approaches are encouraged.  Research projects should focus on oral diseases caused by, but that are not limited to the following viruses: Human Immunodeficiency Virus, Herpes Simplex Virus, Human Papillomavirus, Kaposi’s sarcoma Virus, Epstein Barr Virus, Polyomaviruses, and Cytomegalovirus. 

BACKGROUND

Epigenetic processes are critical for normal development and functioning of healthy individuals.  Epigenomics involves heritable changes in phenotype and gene expression that may be stable over extended time, carry over numerous cell divisions, or may be inherited through many generations without changes to the primary DNA sequence; it refers to external gene and chromatin modifications that affect their transcriptional activation or repression.  Genetic variation occurs due to changes in the primary DNA sequence of genes or by dynamic epigenomic modifications, both of which affect gene activity and expression profiles.  Epigenomic changes mainly occur at two levels: 1) directly, causing DNA modifications; and         2) indirectly, introducing chromatin epigenetic marks that alter the way it is packaged and defines its accessibility to the cellular transcriptional machinery.  However, epigenomic changes can also be introduced by other molecules such as non-coding RNAs.

Viral-induced, host epigenetic perturbations have been reported in human diseases.  For instance, viral pathogenicity and life cycle events can induce epigenetic alterations in host genomes, and the implications of these for causing abnormal cellular processes and generating oral diseases are not well understood.  Similarly, knowledge of epigenetic changes that occur in the genome of oral viruses has been reported, but it is not completely understood.  For example, viral latency, reactivation and lytic replication associated with epigenetic changes and their frequencies are unknown.  Therefore, it is fundamental to understand host and viral epigenomic profiles as well as epigenetic marks and mechanisms involved in changes linked to oral diseases.  These findings will guide the development of novel therapeutic modalities for improving oral health. 

Examples of research topics supported by this initiative include but are not limited to:

  • Mechanisms by which host epigenomic modifications regulate viral pathogenicity and viral interactions with oral cells and tissues
  • Role of epigenomic changes that occur in the genome of oral viruses, and in oral cells and tissues, resulting in oral lesions and diseases
  • Mechanisms of epigenetic reprogramming of host genes by oral viral life cycle events and impact on cellular processes and induction of oral diseases
  • Integration of disease-associated oral viral- and host-epigenomic marks into the Human Epigenome Browser to guide translational and clinical research
  • Generation of genome-wide epigenetic maps, marks, or other related regulatory elements in normal and oral disease cell types
  • Effect of therapeutics on altering epigenetic marks of oral viruses, pathogenicity and induction of oral diseases

Share This Page

GooglePlusExternal link – please review our disclaimer

LinkedInExternal link – please review our disclaimer

Print

This page last updated: February 26, 2014