TY  - JOUR
A1  - Siegl, Christine
A1  - Prusty, Bhupesh K.
A1  - Karunakaran, Karthika
A1  - Wischhusen, Jörg
A1  - Rudel, Thomas
T1  - Tumor Suppressor p53 Alters Host Cell Metabolism to Limit Chlamydia trachomatis Infection
JF  - Cell Reports
N2  - Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.
KW  - chlamydia trachomatis
KW  - tumor
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118200
SN  - 2211-1247
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Rudel, Thomas
A1  - Prusty, Bhupesh K.
A1  - Siegl, Christine
A1  - Gulve, Nitish
A1  - Mori, Yasuko
T1  - GP96 Interacts with HHV-6 during Viral Entry and Directs It for Cellular Degradation
N2  - CD46 and CD134 mediate attachment of Human Herpesvirus 6A (HHV-6A) and HHV-6B to host cell, respectively. But many cell types interfere with viral infection through rapid degradation of viral DNA. Hence, not all cells expressing these receptors are permissive to HHV-6 DNA replication and production of infective virions suggesting the involvement of additional factors that influence HHV-6 propagation. Here, we used a proteomics approach to identify other host cell proteins necessary for HHV-6 binding and entry. We found host cell chaperone protein GP96 to interact with HHV-6A and HHV-6B and to interfere with virus propagation within the host cell. In human peripheral blood mononuclear cells (PBMCs), GP96 is transported to the cell surface upon infection with HHV-6 and interacts with HHV-6A and -6B through its C-terminal end. Suppression of GP96 expression decreased initial viral binding but increased viral DNA replication. Transient expression of human GP96 allowed HHV-6 entry into CHO-K1 cells even in the absence of CD46. Thus, our results suggest an important role for GP96 during HHV-6 infection, which possibly supports the cellular degradation of the virus.
KW  - host cells
KW  - immunoprecipitation
KW  - HeLa cells
KW  - antibodies
KW  - cell binding
KW  - viral transmission and infection
KW  - viral entry
KW  - flow cytometry
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111068
ER  -