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