PMID- 9122239
OWN - NLM
STAT- MEDLINE
DCOM- 19970424
LR  - 20240214
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 94
IP  - 6
DP  - 1997 Mar 18
TI  - Insertion of the adenoviral E3 region into a recombinant viral vector prevents 
      antiviral humoral and cellular immune responses and permits long-term gene 
      expression.
PG  - 2587-92
AB  - Recombinant adenoviruses (Ads) are highly efficient at transferring foreign genes 
      to the liver in vivo; however, the duration of gene expression is limited by the 
      host antiviral immune response, which prevents expression upon readministration 
      of the virus. To test whether overexpression of the immunomodulatory products of 
      the early Ad genome region 3 (E3) could prevent the antiviral immune response and 
      prolong expression of foreign genes delivered by Ad vectors, we injected a 
      recombinant Ad (Ad-E3-hBUGT), containing both E3 and the human 
      bilirubin-uridine-diphosphoglucuronate-glucuronosyltransferase (BUGT) genes, into 
      BUGT-deficient hyperbilirubinemic Gunn rats. Control Gunn rats received Ad-hBUGT, 
      which expresses human BUGT alone. An initial injection of either virus resulted 
      in hepatic expression of human BUGT as evidenced by excretion of bilirubin 
      glucuronides in bile and a reduction of mean serum bilirubin levels from 7.0 
      mg/dl to 1.9-2.7 mg/dl within 7 days. In Ad-E3-hBUGT-injected rats, serum 
      bilirubin levels increased to 4.5 mg/dl by 84 days after infection, but a second 
      administration of the virus on that day resulted in a hypobilirubinemic response 
      similar to that seen with the first injection. In contrast, rats receiving 
      Ad-hBUGT had serum bilirubin levels of 7 mg/dl on day 84 after infection, but 
      showed no reduction of serum bilirubin by reinjection of the virus on that day. 
      In the rats injected with Ad-E3-hBUGT, but not in the ones injected with 
      Ad-hBUGT, there was a marked inhibition of the antiviral antibody and Ad-specific 
      cytotoxic T lymphocyte responses. This is the first demonstration that insertion 
      of E3 genes in recombinant Ads facilitates readministration of a functional 
      vector for long-term correction of an inherited metabolic disorder.
FAU - Ilan, Y
AU  - Ilan Y
AD  - Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, 
      USA.
FAU - Droguett, G
AU  - Droguett G
FAU - Chowdhury, N R
AU  - Chowdhury NR
FAU - Li, Y
AU  - Li Y
FAU - Sengupta, K
AU  - Sengupta K
FAU - Thummala, N R
AU  - Thummala NR
FAU - Davidson, A
AU  - Davidson A
FAU - Chowdhury, J R
AU  - Chowdhury JR
FAU - Horwitz, M S
AU  - Horwitz MS
LA  - eng
GR  - R01 DK046057/DK/NIDDK NIH HHS/United States
GR  - R01 DK039137/DK/NIDDK NIH HHS/United States
GR  - P30 DK041296/DK/NIDDK NIH HHS/United States
GR  - R01-DK 46057/DK/NIDDK NIH HHS/United States
GR  - T32 DK007218/DK/NIDDK NIH HHS/United States
GR  - P30 CA013330/CA/NCI NIH HHS/United States
GR  - R01-DK 39137/DK/NIDDK NIH HHS/United States
GR  - P30-DK 41296/DK/NIDDK NIH HHS/United States
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 (Adenovirus E3 Proteins)
RN  - 27071-67-6 (bilirubin glucuronate)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - *Adenoviridae
MH  - Adenovirus E3 Proteins/biosynthesis/*genetics/*immunology
MH  - Animals
MH  - Antibody Formation
MH  - Bile/metabolism
MH  - Bilirubin/analogs & derivatives/blood/metabolism
MH  - Genetic Therapy/methods
MH  - Genetic Vectors
MH  - Glucuronosyltransferase/biosynthesis/genetics
MH  - Humans
MH  - Hyperbilirubinemia/*immunology/physiopathology/*therapy
MH  - Immunity, Cellular
MH  - Inflammation
MH  - Liver/enzymology/pathology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Time Factors
PMC - PMC20132
EDAT- 1997/03/18 00:00
MHDA- 1997/03/18 00:01
PMCR- 1997/09/18
CRDT- 1997/03/18 00:00
PHST- 1997/03/18 00:00 [pubmed]
PHST- 1997/03/18 00:01 [medline]
PHST- 1997/03/18 00:00 [entrez]
PHST- 1997/09/18 00:00 [pmc-release]
AID - 3873 [pii]
AID - 10.1073/pnas.94.6.2587 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2587-92. doi: 10.1073/pnas.94.6.2587.