Target intelligence / Profile preview

Human immunodeficiency virus type 1 integrase–viral DNA intasome (HIV-1 IN intasome) (HIV-1 IN intasome)

Target
HIV-1 IN intasome
Molecular classification
Enzyme, Other
01

Overview

The Human immunodeficiency virus type 1 (HIV-1) integrase–viral DNA intasome is a specialized nucleoprotein complex that plays a critical role in the viral life cycle by facilitating the integration of viral genetic material into the host cell genome (Passos et al., 2017, Science). This complex is composed of a multimeric assembly of the viral integrase (IN) enzyme—typically a tetramer or higher-order oligomer—bound to the ends of the blunt-ended viral DNA (vDNA) produced during reverse transcription (Engelman & Cherepanov, 2012, Nature Reviews Microbiology). The intasome's primary function is to catalyze the strand transfer reaction, where it inserts the viral DNA into the host's chromosomal DNA, a step that is essential for establishing a productive and permanent infection (Craigie & Bushman, 2012, Cold Spring Harbor Perspectives in Medicine). Because integration is a unique and vital step for HIV-1, the intasome serves as the primary pharmacological target for Integrase Strand Transfer Inhibitors (INSTIs), which are a cornerstone of modern antiretroviral therapy (Hare et al., 2010, Nature). These drugs, including dolutegravir and bictegravir, bind specifically to the metal-ion-containing active site of the intasome, effectively blocking the attachment of host DNA and halting viral replication (Anstett et al., 2017, Current Opinion in HIV and AIDS).

Other names
HIV-1 intasomeIntegrase-DNA complexHIV-1 IN-vDNA complexPre-integration complex core
02

Mechanism of action

Integrase strand transfer inhibition (INSTI), which prevents the covalent insertion of viral DNA into the host cell genome by binding to the intasome active site.

03

Biological functions

Other
04

Disease associations

Infection
05

Safety considerations

Emergence of drug resistance mutationsNeuropsychiatric adverse eventsWeight gainPotential for cross-resistance within the INSTI class
06

Interacting drugs

Raltegravir

4 more in the full profile.

07

Biomarkers

HIV-1 RNA viral loadCD4+ T-cell countIntegrase resistance mutations (e.g., N155H, Q148H/R/K, Y143R/C/H)

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