Related Experiment Video

Updated: Jul 20, 2026

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
13:07

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Published on: January 30, 2019

Inhibition of HIV-1 replication by simian restriction factors, TRIM5alpha and APOBEC3G

R Sakuma1, J A Noser, S Ohmine

  • 1Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Gene Therapy
|September 1, 2006
PubMed

Insights

Simian TRIM5alpha and APOBEC3G show potential for AIDS gene therapy. Engineered T cells expressing these proteins effectively block human immunodeficiency virus type 1 (HIV-1) replication.

Area of Science:

  • Virology
  • Gene Therapy
  • Immunology

Background:

  • Old World monkey TRIM5alpha protein targets incoming human immunodeficiency virus type 1 (HIV-1) viral capsid.
  • The apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC)3 family of proteins hypermutate and degrade viral sequences.

Purpose of the Study:

  • To investigate the potential of simian TRIM5alpha and APOBEC3G as therapeutic sequences for acquired immunodeficiency syndrome (AIDS) gene therapy.
  • To evaluate the efficacy of rhesus and African green monkey (agm) TRIM5alpha in restricting HIV-1 vectors from different subtypes.

Main Methods:

  • Genetic engineering of human T cells to express African green monkey (agm)-TRIM5alpha.
  • Co-expression of agm-APOBEC3G and agm-TRIM5alpha in human T cells.
  • Assessment of HIV-1 replication in engineered T cells.

Main Results:

  • Both rhesus and African green monkey (agm) TRIM5alpha efficiently restricted HIV-1 vectors with divergent Gag proteins.
  • Human T cells engineered to express agm-TRIM5alpha blocked or delayed HIV-1 replication.
  • Co-expression of agm-APOBEC3G and agm-TRIM5alpha successfully blocked HIV-1 replication for over 5 weeks, whereas agm-APOBEC3G alone only transiently suppressed replication.

Conclusions:

  • Simian TRIM5alpha and APOBEC3G are promising candidates for AIDS gene therapy.
  • The combined expression of agm-TRIM5alpha and agm-APOBEC3G provides robust and sustained inhibition of HIV-1 replication.

More Related Videos

Development of Cell-type specific anti-HIV gp120 aptamers for siRNA delivery13:47

Development of Cell-type specific anti-HIV gp120 aptamers for siRNA delivery

Published on: June 23, 2011

A High-throughput Cre-Lox Activated Viral Membrane Fusion Assay to Identify Inhibitors of HIV-1 Viral Membrane Fusion07:22

A High-throughput Cre-Lox Activated Viral Membrane Fusion Assay to Identify Inhibitors of HIV-1 Viral Membrane Fusion

Published on: August 14, 2018

Related Concept Videos

Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

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 retrovirus to...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...