Generation of Lymphocyte Cell Lines Coexpressing CD4 and Wild-Type or Mutant HIV Type 1 Glycoproteins: Implications for HIV Type 1 Env-Induced Cell Lysis

1996 ◽  
Vol 12 (9) ◽  
pp. 783-792 ◽  
Author(s):  
UTE KRÜGER ◽  
TANYA PFEIFFER ◽  
VALERIE BOSCH
1997 ◽  
Vol 13 (9) ◽  
pp. 751-757 ◽  
Author(s):  
MINGXU GUAN ◽  
GABRIELA TUDOR ◽  
JYH-YUAN YANG ◽  
EARL E. HENDERSON

1998 ◽  
Vol 72 (2) ◽  
pp. 1165-1170 ◽  
Author(s):  
Cynthia A. Pise-Masison ◽  
Kyeong-Sook Choi ◽  
Michael Radonovich ◽  
Jürgen Dittmer ◽  
Seong-Jin Kim ◽  
...  

ABSTRACT Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia. HTLV-1 transforms lymphocytes, and there is increasing evidence that the virus-encoded protein, Tax, plays a primary role in viral transformation. We have shown that wild-type p53 in HTLV-1-transformed cells is stabilized. This study was initiated to directly analyze whether the p53 in HTLV-1-transformed cell lines was transcriptionally active and to identify the viral gene product responsible for stabilization and inactivation. Transfection experiments using a p53-responsive reporter plasmid and γ-irradiation studies demonstrate that the wild-type p53 in HTLV-1-transformed cell lines is not fully active. Further, we demonstrate that the HTLV-1-transforming protein, Tax, stabilizes and inactivates p53 function. Cotransfection of Tax with p53 results in a greater than 10-fold reduction in p53 transcription activity. Using Gal4-p53 fusion proteins, we demonstrate that Tax inhibition of p53 transactivation function is independent of sequence-specific DNA binding. Moreover, Tax inhibits p53 function by interfering with the activity of the N-terminal activation domain (amino acids 1 to 52). We conclude that Tax is involved in the inactivation of p53 function and stabilization of p53 in HTLV-1-infected cells. The functional interference of p53 function by Tax may be important for transformation and leukemogenesis.


1995 ◽  
Vol 11 (6) ◽  
pp. 713-717 ◽  
Author(s):  
BLUMA G. BRENNER ◽  
YUZHEN TAO ◽  
ELEENA PEARSON ◽  
ISRAEL REMER ◽  
MARK A. WAINBERG

1997 ◽  
Vol 13 (7) ◽  
pp. 533-543 ◽  
Author(s):  
JAMES E. DRUMMOND ◽  
PHOEBE MOUNTS ◽  
ROBERT J. GORELICK ◽  
JOSE R. CASAS-FINET ◽  
WILLIAM J. BOSCHE ◽  
...  

2002 ◽  
Vol 46 (7) ◽  
pp. 2249-2253 ◽  
Author(s):  
Akhteruzzaman Molla ◽  
Hongmei Mo ◽  
Sudthida Vasavanonda ◽  
Lixin Han ◽  
C. Thomas Lin ◽  
...  

ABSTRACT The in vitro inhibition of wild-type human immunodeficiency virus (HIV) by combinations of lopinavir and six other protease inhibitors over a range of two-drug combination ratios was evaluated. Combinations of lopinavir with indinavir, nelfinavir, amprenavir, tipranavir, and BMS-232632 generally displayed an additive relationship. In contrast, a consistent, statistically significant synergistic inhibition of HIV type 1 replication with combinations of lopinavir and saquinavir was observed. Analysis of the combination indices indicated that lopinavir with saquinavir was synergistic over the entire range of drug combination ratios tested and at all levels of inhibition in excess of 40%. Cellular toxicity was not observed at the highest drug concentrations tested. These results suggest that administration of combinations of the appropriate dose of lopinavir with other protease inhibitors in vivo may result in enhanced antiviral activity with no associated increase in cellular cytotoxicity. More importantly, the observed in vitro synergy between lopinavir and saquinavir provides a theoretical basis for the clinical exploration of a novel regimen of lopinavir-ritonavir and saquinavir.


1996 ◽  
Vol 12 (17) ◽  
pp. 1615-1622 ◽  
Author(s):  
VALÉRIE GIORDANENGO ◽  
MARTINE LIMOUSE ◽  
ALAIN DOGLIO ◽  
JOSETTE LESIMPLE ◽  
JEAN-CLAUDE LEFEBVRE

1995 ◽  
Vol 11 (12) ◽  
pp. 1487-1493 ◽  
Author(s):  
SUNGAE CHO ◽  
THOMAS J. KINDT ◽  
TONG-MAO ZHAO ◽  
SANSANA SAWASDIKOSOL ◽  
BISHOP F. HAGUE

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