PMID- 8650221
OWN - NLM
STAT- MEDLINE
DCOM- 19960725
LR  - 20191210
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 93
IP  - 12
DP  - 1996 Jun 11
TI  - Human immunodeficiency virus tat gene transfer to the murine central nervous 
      system using a replication-defective herpes simplex virus vector stimulates 
      transforming growth factor beta 1 gene expression.
PG  - 6073-8
AB  - The high incidence of neurological disorders in patients afflicted with acquired 
      immunodeficiency syndrome (AIDS) may result from human immunodeficiency virus 
      type 1 (HIV-1) induction of chemotactic signals and cytokines within the brain by 
      virus-encoded gene products. Transforming growth factor beta1 (TGF-beta1) is an 
      immunomodulator and potent chemotactic molecule present at elevated levels in 
      HIV-1-infected patients, and its expression may thus be induced by viral 
      trans-activating proteins such as Tat. In this report, a replication-defective 
      herpes simplex virus (HSV)-1 tat gene transfer vector, dSTat, was used to 
      transiently express HIV-1 Tat in glial cells in culture and following 
      intracerebral inoculation in mouse brain in order to directly determine whether 
      Tat can increase TGF-beta1 mRNA expression. dSTat infection of Vero cells 
      transiently transfected by a panel of HIV-1 long terminal repeat deletion mutants 
      linked to the bacterial chloramphenicol acetyltransferase reporter gene 
      demonstrated that vector-expressed Tat activated the long terminal repeat in a 
      trans-activation response element-dependent fashion independent of the 
      HSV-mediated induction of the HIV-1 enhancer, or NF-kappaB domain. Northern blot 
      analysis of human astrocytic glial U87-MG cells transfected by dSTat vector DNA 
      resulted in a substantial increase in steady-state levels of TGF-beta1 mRNA. 
      Furthermore, intracerebral inoculation of dSTat followed by Northern blot 
      analysis of whole mouse brain RNA revealed an increase in levels of TGF-beta1 
      mRNA similar to that observed in cultured glial cells transfected by dSTat DNA. 
      These results provided direct in vivo evidence for the involvement of HIV-1 Tat 
      in activation of TGF-beta1 gene expression in brain. Tat-mediated stimulation of 
      TGF-beta1 expression suggests a novel pathway by which HIV-1 may alter the 
      expression of cytokines in the central nervous system, potentially contributing 
      to the development of AIDS-associated neurological disease.
FAU - Rasty, S
AU  - Rasty S
AD  - Department of Molecular Genetics and Biochemistry, University of Pittsburgh 
      School of Medicine, PA 15261, USA.
FAU - Thatikunta, P
AU  - Thatikunta P
FAU - Gordon, J
AU  - Gordon J
FAU - Khalili, K
AU  - Khalili K
FAU - Amini, S
AU  - Amini S
FAU - Glorioso, J C
AU  - Glorioso JC
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism/virology
MH  - Chlorocebus aethiops
MH  - Defective Viruses/genetics/physiology
MH  - *Gene Expression Regulation, Viral
MH  - Gene Transfer Techniques
MH  - *Genes, tat
MH  - HIV-1/genetics
MH  - Herpesvirus 1, Human/*genetics/physiology
MH  - Mice
MH  - RNA, Messenger/genetics/metabolism
MH  - Transforming Growth Factor beta/*genetics
MH  - Vero Cells
MH  - Virus Replication/physiology
PMC - PMC39191
EDAT- 1996/06/11 00:00
MHDA- 1996/06/11 00:01
PMCR- 1996/12/11
CRDT- 1996/06/11 00:00
PHST- 1996/06/11 00:00 [pubmed]
PHST- 1996/06/11 00:01 [medline]
PHST- 1996/06/11 00:00 [entrez]
PHST- 1996/12/11 00:00 [pmc-release]
AID - 10.1073/pnas.93.12.6073 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6073-8. doi: 
      10.1073/pnas.93.12.6073.