scholarly journals CD4 antigen-based antireceptor peptides inhibit infectivity of human immunodeficiency virus in vitro at multiple stages of the viral life cycle.

1989 ◽  
Vol 86 (18) ◽  
pp. 7139-7143 ◽  
Author(s):  
P. L. Nara ◽  
K. M. Hwang ◽  
D. M. Rausch ◽  
J. D. Lifson ◽  
L. E. Eiden
Keyword(s):  
Human Immunodeficiency Virus ◽  
Life Cycle ◽  
Viral Life Cycle ◽  
Immunodeficiency Virus ◽  
Multiple Stages

scholarly journals Heterocyclic Compounds That Inhibit Rev-RRE Function and Human Immunodeficiency Virus Type 1 Replication

2008 ◽  
Vol 52 (9) ◽  
pp. 3169-3179 ◽  
Author(s):  
Deidra Shuck-Lee ◽  
Fei Fei Chen ◽  
Ryan Willard ◽  
Sharmila Raman ◽  
Roger Ptak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Life Cycle ◽  
Cell Line ◽  
Particle Production ◽  
Screening Assay ◽  
Rev Response Element ◽  
Immunodeficiency Virus ◽  
A Cell ◽  
Viruslike Particles

ABSTRACT A cell-based screening assay was performed to identify compounds that inhibited the postintegration stage of the human immunodeficiency virus (HIV) life cycle. This assay utilized a cell line that contains the HIV gag and pol genes expressed in a Rev-dependent fashion. The cell line produces about 10 to 15 ng of p24 per milliliter of medium over a 24-h period in the form of viruslike particles. Any compound that inhibits a postintegration step in the HIV life cycle scores in this assay by decreasing particle production. Forty thousand compounds were screened, and 192 compounds were selected from the original screen because they showed more than 50% inhibition at a 10 μM concentration. The cumulative evidence presented in this study strongly suggests that 2 of the 192 compounds work as inhibitors of HIV Rev function. This was determined by a variety of cell-based assays, although the compounds do not interfere with Rev-RRE (Rev response element) binding in vitro. Both compounds inhibit replication of the lab isolate NL4-3 as well as an HIV primary isolate from Brazil (93BR021) and thus are promising leads as therapeutic candidates that target HIV replication through inhibition of Rev function.

scholarly journals The 5′ and 3′ TAR Elements of Human Immunodeficiency Virus Exert Effects at Several Points in the Virus Life Cycle

1998 ◽  
Vol 72 (11) ◽  
pp. 9217-9223 ◽  
Author(s):  
Atze T. Das ◽  
Bep Klaver ◽  
Ben Berkhout
Keyword(s):  
Human Immunodeficiency Virus ◽  
Life Cycle ◽  
Reverse Transcription ◽  
Wild Type ◽  
Rna Packaging ◽  
Virus Life Cycle ◽  
Activation Of Transcription ◽  
Immunodeficiency Virus

ABSTRACT The human immunodeficiency virus type 1 RNA genome contains a terminal repeat (R) sequence that encodes the TAR hairpin motif, which has been implicated in Tat-mediated activation of transcription. More recently, a variety of other functions have been proposed for this structured RNA element. To determine the replicative roles of the 5′ and 3′ TAR hairpins, we analyzed multiple steps in the life cycle of wild-type and mutant viruses. A structure-destabilizing mutation was introduced in either the 5′, the 3′, or both TAR motifs of the proviral genome. As expected, opening of the 5′ TAR hairpin caused a transcription defect. Because the level of protein expression was not similarly reduced, the translation of this mRNA was improved. No effect of the 3′ hairpin on transcription and translation was measured. Mutations of the 5′ and 3′ hairpin structures reduced the efficiency of RNA packaging to similar extents, and RNA packaging was further reduced in the 5′ and 3′ TAR double mutant. Upon infection of cells with these virions, a reduced amount of reverse transcription products was synthesized by the TAR mutant. However, no net reverse transcription defect was observed after correction for the reduced level of virion RNA. This result was confirmed in in vitro reverse transcription assays. These data indicate that the 5′ and 3′ TAR motifs play important roles in several steps of the replication cycle, but these structures have no significant effect on the mechanism of reverse transcription.

scholarly journals Interaction of the Human Immunodeficiency Virus Type 1 Nucleocapsid with Actin

1999 ◽  
Vol 73 (4) ◽  
pp. 2901-2908 ◽  
Author(s):  
Bindong Liu ◽  
Renke Dai ◽  
Chun-Juan Tian ◽  
Liza Dawson ◽  
Robert Gorelick ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Life Cycle ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Life Cycle ◽  
Wild Type Virus ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The nucleocapsid (NC) domain of the retrovirus Gag protein plays several important roles in the viral life cycle, including virus assembly, viral genomic RNA encapsidation, primer tRNA placement, and enhancement of viral reverse transcription. In this study, deletion of NC domain of human immunodeficiency virus type 1 (HIV-1) Gag was found to drastically reduce virus particle production in CD4+ T cells. Cellular fractionation experiments showed that although most of the uncleaved wild-type HIV-1 Gag, unmyristylated Gag, and p6Gag domain-truncated Gag molecules copurified with the host cell cytoskeleton, most of the mutant Gag molecules lacking both the NC and p6Gag domains failed to cofractionate with cytoskeleton. In wild-type virus-infected cells, in which the viral protease was active, the cleaved NCp7 copurified with the cytoskeleton, whereas most of the MAp17 and CAp24 did not. Monoclonal antibody against actin coimmunoprecipitated full-length Gag and p6Gag domain-truncated Gag molecules from cell lysates but failed to precipitate the truncated mutant Gag molecules lacking NC plus p6Gag. Purified recombinant NCp7, but not CAp24, was able to bind F-actin in cosedimentation experiments. Furthermore, wild-type NCp7 and a zinc finger mutant NCp7(F16A), like a cellular actin-binding protein (the villin headpiece), bound F-actin in a dose-dependent fashion in vitro. Taken together, these results suggest that HIV-1 NCp7 can bind F-actin directly and that interaction between HIV-1 Gag and the actin cytoskeleton through the NC domain may play an important role in HIV-1 assembly and/or other steps of the viral life cycle.

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