1. A Distinct Temporal Regulation of Cellular
Bcl-2 Family Proteins Promotes Survival of
HCMV-Infected Monocytes
Donna Collins-McMillen, E.V. Stevenson, M.T. Nogalski, J. Caskey,
G.C.T. Chan, and A.D. Yurochko
Louisiana State University Health – Shreveport, LA
6. HCMV Engages a Distinct Pro-Survival
Mechanism to Prevent Monocyte
Apoptosis
1) Bi-phasic regulation of Mcl-1 and Bcl-2
2) Distinct & overlapping signaling through
EGFR/integrins
3) Promotes survival at multiple apoptotic checkpoints
• bypasses viability checkpoint at 48 h (stabilizes Mcl-1,
Chan et al., 2010)
• adapts to anti-viral pro-apoptotic response (Bcl-2 up in
response to Bax)
7. Bi-Phasic Mcl-1/Bcl-2 Shift
Mcl-1 in HCMV-infected monocytes
MФmonocyte 48hpi
Mcl-1 Bcl-2
(1) (1.2)(1.4) (3.9)(1.9)(5.1) (2.0) (6.2))
Bcl-2 in HCMV-infected monocytesChan et al., 2010
8. Bi-Phasic Mcl-1/Bcl-2 Shift
• Bcl-2 controls late survival in HCMV-infected monocytes
(Mcl-1 early, Chan et al., 2010)
• Mcl-1 and Bcl-2 are both required for early survival in mock-
infected cells
14. Acknowledgements
Mentor
Dr. Andrew Yurochko
Dissertation Committee
Dr. Robert Chervenak
Dr. Lindsey Hutt-Fletcher
Dr. Dennis O’Callaghan
Dr. Kelly Tatchell
Dr. Felicia Goodrum (U of AZ)
Funding:
Yurochko Lab
Liesl Milford
Dr. Maciej Nogalski
Dr. Gary Chan
Dr. Emily Stevenson
Dr. Yanjie Li
Stephen Cieply
Dr. Jung Heon Kim
Joshua Caskey
A156077
P30GM110703
Pre-Doctoral Fellowship
14PRE20310027