PMID- 17928352
OWN - NLM
STAT- MEDLINE
DCOM- 20080124
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 82
IP  - 2
DP  - 2008 Jan
TI  - The U95 protein of human herpesvirus 6B interacts with human GRIM-19: silencing 
      of U95 expression reduces viral load and abrogates loss of mitochondrial membrane 
      potential.
PG  - 1011-20
AB  - To better understand the pathogenesis of human herpesvirus 6 (HHV-6), it is 
      important to elucidate the functional aspects of immediate-early (IE) genes at 
      the initial phase of the infection. To study the functional role of the HHV-6B IE 
      gene encoding U95, we generated a U95-Myc fusion protein and screened a 
      pretransformed bone marrow cDNA library for U95-interacting proteins, using 
      yeast-two hybrid analysis. The most frequently appearing U95-interacting protein 
      identified was GRIM-19, which belongs to the family of genes associated with 
      retinoid-interferon mortality and serves as an essential component of the 
      oxidative phosphorylation system. This interaction was verified by both 
      coimmunoprecipitation and confocal microscopic coimmunolocalization. Short-term 
      HHV-6B infection of MT-4 T-lymphocytic cells induced syncytial formation, 
      resulted in decreased mitochondrial membrane potential, and led to progressively 
      pronounced ultrastructural changes, such as mitochondrial swelling, myelin-like 
      figures, and a loss of cristae. Compared to controls, RNA interference against 
      U95 effectively reduced the U95 mRNA copy number and abrogated the loss of 
      mitochondrial membrane potential. Our results indicate that the high affinity 
      between U95 early viral protein and GRIM-19 may be closely linked to the 
      detrimental effect of HHV-6B infection on mitochondria. These findings may 
      explain the alternative cell death mechanism of expiration, as opposed to 
      apoptosis, observed in certain productively HHV-6B-infected cells. The 
      interaction between U95 and GRIM-19 is thus functionally and metabolically 
      significant in HHV-6B-infected cells and may be a means through which HHV-6B 
      modulates cell death signals by interferon and retinoic acid.
FAU - Yeo, W M
AU  - Yeo WM
AD  - Human Genome Laboratory, Department of Microbiology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Kent Ridge 117597, Singapore.
FAU - Isegawa, Yuji
AU  - Isegawa Y
FAU - Chow, Vincent T K
AU  - Chow VT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071010
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (U95 protein, human herpesvirus 6B)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 1.6.5.- (NDUFA13 protein, human)
SB  - IM
MH  - Apoptosis Regulatory Proteins/*metabolism
MH  - Cell Line
MH  - Gene Silencing
MH  - Giant Cells/virology
MH  - Herpesvirus 6, Human/genetics/*physiology
MH  - Humans
MH  - Immediate-Early Proteins/antagonists & inhibitors/*metabolism
MH  - Immunoprecipitation
MH  - Membrane Potential, Mitochondrial/*physiology
MH  - Microscopy, Confocal
MH  - Mitochondria/ultrastructure
MH  - Mitochondrial Swelling
MH  - NADH, NADPH Oxidoreductases/*metabolism
MH  - Protein Binding
MH  - Two-Hybrid System Techniques
MH  - *Viral Load
PMC - PMC2224593
EDAT- 2007/10/12 09:00
MHDA- 2008/01/25 09:00
PMCR- 2008/05/01
CRDT- 2007/10/12 09:00
PHST- 2007/10/12 09:00 [pubmed]
PHST- 2008/01/25 09:00 [medline]
PHST- 2007/10/12 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - JVI.01156-07 [pii]
AID - 1156-07 [pii]
AID - 10.1128/JVI.01156-07 [doi]
PST - ppublish
SO  - J Virol. 2008 Jan;82(2):1011-20. doi: 10.1128/JVI.01156-07. Epub 2007 Oct 10.