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Updated: May 1, 2026
Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
Incorporation of mouse APOBEC3 into murine leukemia virus virions decreases the activity and fidelity of reverse
Stefano Boi1, Angelo Kolokithas2, Joyce Shepard2
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA Department of Biomedical Sciences, University of Cagliari, Monserrato (Cagliari), Italy.
Abstract:
APOBEC3 proteins are restriction factors that induce G→A hypermutation in retroviruses during replication as a result of cytidine deamination of minus-strand DNA transcripts. However, the mechanism of APOBEC inhibition of murine leukemia viruses (MuLVs) does not appear to be G→A hypermutation and is unclear. In this report, the incorporation of mA3 in virions resulted in a loss in virion reverse transcriptase (RT) activity and RT fidelity that correlated with the loss of virion-specific infectivity.
Insights
APOBEC3 (A3) proteins restrict retroviruses by deaminating DNA. However, A3 inhibits murine leukemia viruses (MuLVs) through an unclear mechanism, not G→A hypermutation, impacting reverse transcriptase activity and infectivity.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- APOBEC3 (A3) proteins are known restriction factors that inhibit retroviral replication.
- A3 proteins function by inducing G→A hypermutation via cytidine deamination of minus-strand DNA transcripts.
- The precise mechanism by which A3 inhibits murine leukemia viruses (MuLVs) remains unclear and does not appear to involve G→A hypermutation.
Purpose of the Study:
- To investigate the mechanism of APOBEC3 inhibition of murine leukemia viruses (MuLVs).
- To determine the effect of APOBEC3 incorporation on MuLV virion properties.
Main Methods:
- Incorporation of a specific APOBEC3 protein (mA3) into MuLV virions.
- Assay of virion reverse transcriptase (RT) activity.
- Assessment of RT fidelity.
- Measurement of virion-specific infectivity.
Main Results:
- Incorporation of mA3 into MuLV virions led to a significant loss of virion reverse transcriptase (RT) activity.
- mA3 incorporation also resulted in a loss of RT fidelity.
- These losses in RT activity and fidelity correlated directly with a reduction in virion-specific infectivity.
Conclusions:
- APOBEC3 proteins inhibit MuLV replication through a mechanism distinct from G→A hypermutation.
- The inhibition involves a detrimental effect on virion reverse transcriptase activity and fidelity.
- This disruption of RT function ultimately leads to decreased MuLV infectivity.
