Related Experiment Video
Updated: Mar 22, 2026
10:34
Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
Published on: February 22, 2017
8.1K
HIV-1 capsid is involved in post-nuclear entry steps
Nan-Yu Chen1,2, Lihong Zhou1,3, Paul J Gane4,5
1Division of Infection and Immunity, University College London, Cruciform Building, 90 Gower Street, London, WC1E 6BT, UK.
Retrovirology
|April 25, 2016
Summary
The antibiotic Coumermycin-A1 (C-A1) inhibits HIV-1 integration by targeting the viral capsid. C-A1 reduces nuclear capsid accumulation and enhances TRIMCyp restriction escape, revealing capsid
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- The human immunodeficiency virus type 1 (HIV-1) capsid protein plays a role in viral uncoating and nuclear import.
- While some HIV-1 capsid is found in the nucleus, its function there remains unclear.
- Previous studies indicated that Coumermycin-A1 (C-A1) inhibits HIV-1 integration, with capsid mutations conferring resistance, suggesting a role in post-nuclear entry.
Purpose of the Study:
- To investigate the role of HIV-1 capsid in post-nuclear entry steps.
- To elucidate the mechanism by which C-A1 inhibits HIV-1 integration.
- To explore the interaction of C-A1 with the HIV-1 capsid and its effect on viral nuclear import and restriction.
Main Methods:
- Molecular docking to predict C-A1 binding sites on the capsid.
- Isothermal titration calorimetry to confirm C-A1 binding to capsid.
- Cyclosporine washout assays in Jurkat CD4+ T cells with engineered human TRIMCyp.
- Sub-cellular fractionation to analyze capsid localization.
- Depletion of Nup153 and assessment of viral susceptibility.
- Analysis of CPSF6 binding to capsid.
Main Results:
- C-A1 inhibits HIV-1 integration in a capsid-dependent manner.
- C-A1 binds to a pocket formed by two adjacent capsid monomers within the hexameric capsid.
- C-A1 accelerates and enhances escape from TRIMCyp restriction.
- C-A1 reduces the accumulation of capsid in the nucleus.
- Mutations in capsid (A105S, N74D) prevent nuclear capsid accumulation, independent of C-A1.
- Nup153 depletion reduces TRIMCyp restriction, suggesting its role in maintaining viral core integrity in the nucleus.
- C-A1 increases the binding of nuclear protein CPSF6 to the capsid.
Conclusions:
- HIV-1 capsid is implicated in crucial steps after nuclear entry and before integration.
- C-A1's mechanism involves capsid interaction, affecting nuclear import and restriction evasion.
- Nup153 plays a role in nuclear import and potentially protects the viral core within the nucleus.
Related Concept Videos
01:10Retrovirus Life Cycles
50.5K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
50.5K
00:56Viral Structure
75.7K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
75.7K
01:26Size and Structure of Viral Genomes
1.0K
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
1.0K
02:33Retroviruses
15.7K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
15.7K
01:34Nuclear Protein Sorting
6.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
6.6K
00:50What are Viruses?
130.2K
Overview
130.2K