Metabolic stress is a barrier to Epstein–Barr virus-mediated B-cell immortalization

Karyn McFadden, Amy Y. Hafeza, Rigel Kishton, Joshua E. Messinger, Pavel A. Nikitin, Jeffrey C. Rathmell and Micah A. Luftiga

Proc Natl Acad Sci U S A. 2016 Feb 9; 113(6):E782-90. doi: 10.1073

Speaker: Chao-Chen Chang (張肇宸)                  Time: 15:10~16:00, Mar 30, 2016

Commentator: Dr. Yao Chang (張堯 老師)         Place: Room 601

Abstract:

Epstein–Barr virus (EBV) is an oncogenic g herpesvirus that infects and immortalizes resting B cells with very high efficiency. EBV triggers a transient period of hyperproliferation and then induces cell cycle arrest in the infected cells. After EBV-induced hyperproliferation in primary B cells, the growth arrested subpopulations were defined as proliferated–arrested (PA) cells, whereas others were defined as proliferated–proliferated (PP) cells. Since the arrest prevents long-term outgrowth of the infected cells (1), the authors speculated that cell senescence may be involved. By evaluating the senescent markers, the authors showed that the growth arresting of PA cell was resulting from senescence. Additionally, senescence is antagonized by autophagy that potentially provides the metabolic intermediates needed for rapid proliferation. They found the PA cells exhibit less efficient autophagic flux when compare to the PP cells. These data suggested that EBV-induced hyperproliferation needs a balanced level of autophagy to produce the biosynthetic intermediates that are required for cell growth and proliferation. Moreover, they found that both the autophagy and mitochondrial respiration were all decreased in EBV-infected PA cells. Besides, the authors found that DNA damage contributes to the cell proliferation restriction in infected cells; but it is resolvable to virus and cell continually proliferation after a transient growth arrest. In conclusion, early EBV-induced B-cell proliferation could be suppressed by the metabolic stress which served as an intrinsic barrier to EBV-mediated B-cell immortalization.

Reference:

1.         Nikitin PA, Price AM, McFadden K, Yan CM, Luftig MA. 2014. Mitogen-Induced B-Cell Proliferation Activates Chk2-Dependent G1/S Cell Cycle Arrest. Plos One 9.