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Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
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Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes

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Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

Mark A Endsley1, Anoma D Somasunderam1, Guangyu Li2

  • 1Department Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.

Virology
|April 15, 2014
PubMed

Insights

ADAM10 protein is crucial for HIV-1 replication by aiding viral nuclear entry in T lymphocytes. Inhibiting ADAM10 processing offers a new strategy to block HIV-1 before it reaches the nucleus.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • ADAM10 is essential for HIV-1 replication in macrophages and cell lines.
  • HIV-1 replication is interrupted prior to nuclear translocation when ADAM10 is silenced.
  • HIV-1 replication also depends on ADAM15 and γ-secretase, which process ADAM10.

Purpose of the Study:

  • To investigate the role of ADAM10 in HIV-1 replication in CD4(+) T lymphocytes.
  • To elucidate the mechanism by which ADAM10 supports HIV-1 replication.
  • To identify ADAM10 as a potential therapeutic target for HIV-1 infection.

Main Methods:

  • Silencing gene expression (ADAM10, ADAM15, γ-secretase).
  • Studying HIV-1 replication in CD4(+) T lymphocytes.
  • Investigating protein interactions using immunoprecipitation and co-localization assays.

Main Results:

  • ADAM10 expression supports HIV-1 replication in CD4(+) T lymphocytes.
  • The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC).
  • ADAM10 ICD co-localizes with HIV-1 integrase within the PIC in the cytoplasm.

Conclusions:

  • ADAM15/γ-secretase processing of ADAM10 releases its ICD.
  • The ICD of ADAM10 is incorporated into the HIV-1 PIC, facilitating nuclear trafficking.
  • ADAM10 represents a novel therapeutic target for blocking HIV-1 replication prior to nuclear entry.
Keywords:
ADAM10ADAM15CD4(+) T lymphocytesHIV-1 integraseHIV-1 pre-integration complex (PIC)HIV-1 replicationMacrophagesγ-Secretase

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