PMID- 10623756
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20190508
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 74
IP  - 2
DP  - 2000 Jan
TI  - Potential role for luman, the cellular homologue of herpes simplex virus VP16
      (alpha gene trans-inducing factor), in herpesvirus latency.
PG  - 934-43
AB  - The cascade of herpes simplex virus (HSV) gene expression that results in viral
      replication begins with the activation of viral immediate-early (IE) genes by the
      virion-associated protein VP16. VP16 on its own is inefficient at associating
      with complexes formed on IE gene promoters and depends upon the cellular factor
      HCF for its activity. In this respect VP16 mimics the host basic leucine zipper
      (bZIP) protein Luman, which also requires HCF for activating transcription. Our
      objective is to explore interactions between Luman and HCF and to determine if
      they play a role in the biology of herpesviruses. In this report we show that in 
      cultured cells ectopically expressed Luman was retained in the cytoplasm, where
      it colocalized with Calnexin, a protein normally associated with the endoplasmic 
      reticulum (ER). Retention of Luman in the ER depends on a hydrophobic segment of 
      the protein that probably serves as a transmembrane domain. Deletion of this
      domain changed the intracellular location of Luman so that most of the mutant
      protein was in the nucleus of cells. While HCF was present in the nucleus of most
      cells, in cells expressing Luman it was retained in the cytoplasm where the two
      proteins colocalized. This cytoplasmic association of Luman and HCF could also be
      demonstrated in neurons in trigeminal ganglia removed from cattle soon after
      death. Cells in tissue culture that expressed Luman, but not a mutant form of the
      protein that fails to bind HCF, were resistant to a productive infection with HSV
      type 1 (HSV-1). We hypothesize that similar Luman-HCF interactions in sensory
      neurons in trigeminal ganglia result in the suppression of viral replication and 
      the establishment of latency. Interestingly, Luman could activate the promoters
      of IE110 and LAT, two genes that are critical for reactivation of HSV-1 from
      latency. This suggests a role for Luman in the reactivation process as well.
FAU - Lu, R
AU  - Lu R
AD  - Department of Veterinary Microbiology, Western College of Veterinary Medicine,
      University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4, Canada.
FAU - Misra, V
AU  - Misra V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CREB3 protein, human)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HCFC1 protein, human)
RN  - 0 (Herpes Simplex Virus Protein Vmw65)
RN  - 0 (Host Cell Factor C1)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (Vmw110 protein, Human herpesvirus 1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Cattle
MH  - Cyclic AMP Response Element-Binding Protein
MH  - Cytoplasm/metabolism
MH  - DNA-Binding Proteins/genetics/metabolism/*physiology
MH  - Gene Expression Regulation, Viral
MH  - HeLa Cells
MH  - Herpes Simplex Virus Protein Vmw65/chemistry
MH  - Herpesvirus 1, Human/*physiology
MH  - Host Cell Factor C1
MH  - Humans
MH  - Immediate-Early Proteins/genetics
MH  - Leucine Zippers
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - Proteins/metabolism
MH  - Rabbits
MH  - Recombinant Fusion Proteins/genetics/metabolism/physiology
MH  - Response Elements
MH  - Transcription Factors/chemistry/genetics/*physiology
MH  - Ubiquitin-Protein Ligases
MH  - Virus Latency/*physiology
PMC - PMC111614
EDAT- 2000/01/07 00:00
MHDA- 2000/01/07 00:01
CRDT- 2000/01/07 00:00
PHST- 2000/01/07 00:00 [pubmed]
PHST- 2000/01/07 00:01 [medline]
PHST- 2000/01/07 00:00 [entrez]
AID - 10.1128/jvi.74.2.934-943.2000 [doi]
PST - ppublish
SO  - J Virol. 2000 Jan;74(2):934-43. doi: 10.1128/jvi.74.2.934-943.2000.