translation agency

NLM AIDSLINE
Inhibition of Human Immunodeficiency Virus integrase by beta-conidendrol.
Lafemina RL; Hazuda DJ; Graham P; Legrow K; Culberson JC; Emini EA;
December 30, 1995
Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:147.

The Human Immunodeficiency Virus type 1 (HIV-1) integrase protein is required for productive virus spread in infected T-lymphoid cells. This suggests that inhibitors of integrase may be useful in controlling the spread of HIV-1 in infected individuals. Integrase protein expressed in E. Coli displays three functions in vitro, when oligonucleotides modelled on the viral termini are used as substrates. These functions are a specific dinucleotide cleavage, a non-specific endonuclease activity, and a strand-transfer activity. We have observed that beta-conidendrol inhibits the specific endonucleolytic function of integrase in vitro with an IC50 of 500 nM. Parallel inhibition of the non-specific cleavage function was also observed, and in the absence of non- specific cleavage, integration products were not detected. Beta-conidendrol also inhibits a modified integrase (C43S) which is notably reduced in its ability to specifically cleave a dinucleotide from the substrate terminus. Beta- conidendrol was modelled as a nucleotide (AMP), and may resemble either the A residue that contributes to the specific cleavage reaction, or an adenylate interacting at a putative allosteric site.

Adult Female Herpes Zoster/*COMPLICATIONS Human HIV Infections/*COMPLICATIONS/EPIDEMIOLOGY HIV Seroprevalence Male Middle Age Prevalence Prospective Studies Retrospective Studies Risk Factors United States/EPIDEMIOLOGY ABSTRACT

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