Frontiers in Immunology
Frontiers in Immunology
5 years ago

Epstein-Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency.

Carrie L Lucas, Jean-Marie Carpier
Activated PI3Kδ Syndrome (APDS) is an inherited immune disorder caused by heterozygous, gain-of-function mutations in the genes encoding the phosphoinositide 3-kinase delta (PI3Kδ) subunits p110δ or p85δ. This recently described primary immunodeficiency disease (PID) is characterized by recurrent sinopulmonary infections, lymphoproliferation, and susceptibility to herpesviruses, with Epstein-Barr virus (EBV) infection being most notable. A broad range of PIDs having disparate, molecularly defined genetic etiology can cause susceptibility to EBV, lymphoproliferative disease, and lymphoma. Historically, PID patients with loss-of-function mutations causing defective cell-mediated cytotoxicity or antigen receptor signaling were found to be highly susceptible to pathological EBV infection. By contrast, the gain of function in PI3K signaling observed in APDS patients paradoxically renders these patients susceptible to EBV, though the underlying mechanisms are incompletely understood. At a cellular level, APDS patients exhibit deranged B lymphocyte development and defects in class switch recombination, which generally lead to defective immunoglobulin production. Moreover, APDS patients also demonstrate an abnormal skewing of T cells toward terminal effectors with short telomeres and senescence markers. Here, we review APDS with a particular focus on how the altered lymphocyte biology in these patients may confer EBV susceptibility.

Publisher URL: http://doi.org/10.3389/fimmu.2017.02005

DOI: 10.3389/fimmu.2017.02005

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.