PMID- 8692823
OWN - NLM
STAT- MEDLINE
DCOM- 19960823
LR  - 20240104
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 93
IP  - 13
DP  - 1996 Jun 25
TI  - A point mutation in the HIV-1 Tat responsive element is associated with 
      postintegration latency.
PG  - 6377-81
AB  - Study of the mechanism of HIV-1 postintegration latency in the ACH2 cell line 
      demonstrates that these cells failed to increase HIV-1 production following 
      treatment with exogenous Tat. Reasoning that the defect in ACH2 cells involves 
      the Tat response, we analyzed the sequence of tat cDNA and Tat responsive element 
      (TAR) from the virus integrated in ACH2. Tat cDNA sequence is closely related to 
      that of HIV LAI, and the encoded protein is fully functional in terms of long 
      terminal repeat (LTR) transactivation. Cloning of a region corresponding to the 
      5'-LTR from ACH2, however, identified a point mutation (C37 -> T) in TAR. This 
      mutation impaired Tat responsiveness of the LTR in transient transfection assays, 
      and the measured defect was complemented in cells that had been treated with 
      tetradecanoyl phorbol acetate or tumor necrosis factor type alpha (TNF-alpha). A 
      compensatory mutation in TAR (G28 -> A), designed to reestablish base pairing in 
      the TAR hairpin, restored wild-type Tat responsiveness. When the (C37 -> T) 
      mutation was introduced in an infectious clone of HIV-1, no viral production was 
      measured in the absence of TNF-alpha, whereas full complementation was observed 
      when the infection was conducted in the presence of TNF-alpha or when a 
      compensatory mutation (G28 -> A) was introduced into TAR. These experiments 
      identify a novel mutation associated with HIV-1 latency and suggest that 
      alterations in the Tat-TAR axis can be a crucial determinant of the latent 
      phenotype in infected individuals.
FAU - Emiliani, S
AU  - Emiliani S
AD  - The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
FAU - Van Lint, C
AU  - Van Lint C
FAU - Fischle, W
AU  - Fischle W
FAU - Paras, P Jr
AU  - Paras P Jr
FAU - Ott, M
AU  - Ott M
FAU - Brady, J
AU  - Brady J
FAU - Verdin, E
AU  - Verdin E
LA  - eng
GR  - GM51671-01A1/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (DNA Primers)
RN  - 0 (Gene Products, tat)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Base Sequence
MH  - DNA Primers
MH  - Gene Products, tat/*genetics
MH  - HIV Long Terminal Repeat
MH  - HIV-1/*genetics/pathogenicity/physiology
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Phenotype
MH  - *Point Mutation
MH  - Proviruses/genetics/pathogenicity/physiology
MH  - Transfection
MH  - Virus Latency/genetics
MH  - Virus Replication/genetics
MH  - tat Gene Products, Human Immunodeficiency Virus
PMC - PMC39030
EDAT- 1996/06/25 00:00
MHDA- 2001/03/28 10:01
PMCR- 1996/12/25
CRDT- 1996/06/25 00:00
PHST- 1996/06/25 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1996/06/25 00:00 [entrez]
PHST- 1996/12/25 00:00 [pmc-release]
AID - 10.1073/pnas.93.13.6377 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6377-81. doi: 
      10.1073/pnas.93.13.6377.