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Human Disorders of PI3K Biology

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Front. Immunol. | doi: 10.3389/fimmu.2018.00237

Herpesviruses in activated PI3K-δ syndrome

  • 1National Institutes of Health (NIH), United States

The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is important for multiple stages of herpesvirus replication including virus entry, replication, latency, and reactivation. Recently, patients with gain-of-function mutations in the p110δ catalytic subunit of PI3K or in the p85 regulatory subunit of PI3K have been reported. These patients have constitutively active PI3K with hyperactivation of Akt. They present with lymphoproliferation and often have infections, particularly recurrent respiratory infections and/or severe virus infections. The most frequent virus infections are due to Epstein-Barr virus (EBV) and cytomegalovirus (CMV); patients often present with persistent EBV and/or CMV viremia, EBV lymphoproliferative disease, or CMV lymphadenitis. No patients have been reported with CMV pneumonia, colitis, or retinitis. Other herpesvirus infections have included herpes simplex pneumonia, recurrent zoster, and varicella after vaccination with the varicella vaccine. Additional viral infections have included adenovirus viremia, severe warts, and extensive molluscum contagiosum virus infection. The increased susceptibility to virus infections in these patients is likely due to reduced numbers of long-lived memory CD8 T cells and increased numbers of terminally differentiated effector CD8 T cells.

Keywords: PI3K, Akt, PIK3CD, PIK3R1, APDs, PASLI, Epstein-Barr virus, Cytomegalovirus

Received: 24 Nov 2017; Accepted: 26 Jan 2018.

Edited by:

Carrie L. Lucas, Yale University, United States

Reviewed by:

Silvia C. Giliani, University of Brescia, Italy
Flore Rozenberg, Université Paris Descartes, France  

Copyright: © 2018 Cohen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jeffrey I. Cohen, National Institutes of Health (NIH), Bethesda, United States, jcohen@niaid.nih.gov