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Updated: Apr 26, 2026
Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
Published on: February 22, 2017
Human APOBEC3F incorporation into human immunodeficiency virus type 1 particles
Xin Wang1, Xiaoyu Li1, Jing Ma2
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
Insights
The APOBEC3F protein
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- APOBEC3 proteins are key antiviral factors against retroviruses, with APOBEC3G (hA3G) and APOBEC3F (hA3F) showing potent anti-HIV-1 activity.
- Efficient antiviral function of hA3F requires its incorporation into HIV-1 virions, but the underlying mechanism is not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms governing the viral packaging of APOBEC3F (hA3F).
- To identify specific regions and residues within HIV-1 Gag and hA3F essential for hA3F virion incorporation.
Main Methods:
- Detailed mapping studies were performed to pinpoint regions within hA3F and HIV-1 Gag involved in virion encapsidation.
- Functional assays were used to assess the role of specific protein domains, linker sequences, and residues in hA3F incorporation.
Main Results:
- The nucleocapsid (NC) domain of HIV-1 Gag and a specific linker sequence (amino acids 104-156) in hA3F are crucial for hA3F viral packaging.
- A cluster of basic residues near the N-terminal zinc finger (ZF) and the inter-ZF linker of HIV-1 NC are important for hA3F incorporation.
- At least one of the two ZFs in HIV-1 NC is necessary for hA3F incorporation, and a fragment of hA3F can compete with both hA3G and hA3F for packaging.
Conclusions:
- Identified specific domains and residues in HIV-1 Gag NC and hA3F that mediate hA3F virion incorporation.
- Suggests a common mechanism for the virion encapsidation of APOBEC3G (hA3G) and APOBEC3F (hA3F) into HIV-1 particles.
- Provides critical insights into the molecular basis of hA3F antiviral activity against HIV-1.
Abstract:
APOBEC3 proteins are a family of cytidine deaminases that exhibit broad antiretroviral activity. Among APOBEC3 proteins, APOBEC3G (hA3G) and APOBEC3F (hA3F) exhibit the most potent anti-HIV-1 activities. Although the incorporation of hA3F into virions is a prerequisite for exerting its antiviral function, the detail mechanism underlying remains incompletely understood. In this work, we present data showing that the nucleocapsid (NC) domain of HIV-1 Gag and a linker sequence between the two cytidine deaminase domains within hA3F, i.e., 104-156 amino acids, are required for viral packaging of hA3F. A detailed mapping study reveals that the cluster of basic residues surrounding the N-terminal zinc finger (ZF) and the linker region between the ZFs of HIV-1 NC play an important role in A3F incorporation, in addition, at least one of two ZFs is required. A hA3F fragment is able to compete with both hA3G and hA3F for viral incorporation, suggesting a common mechanism underlying virion encapsidation of hA3G and hA3F. Taken together, these results shed a light on the detail mechanism underlying viral incorporation of hA3F.
