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Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
HIV restriction by APOBEC3 in humanized mice.
John F Krisko1, Francisco Martinez-Torres, John L Foster
1Division of Infectious Diseases, Department of Internal Medicine, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America. john_foster@med.unc.edu
Plos Pathogens
|April 5, 2013
Summary
The APOBEC3 immune system restricts HIV, but CXCR4-tropic HIV can evade this defense in specific thymic cells. CCR5-tropic HIV is largely inactivated without the viral infectivity factor (vif).
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Innate immune restriction factors, like APOBEC3, are crucial barriers against zoonotic virus transmission.
- The APOBEC3 (A3G, A3F) family of enzymes restricts viruses including HIV, which counteracts them with its Vif protein.
- Understanding these interactions is key to developing antiviral therapies.
Purpose of the Study:
- To investigate APOBEC3 restriction of different HIV tropisms (CCR5-tropic vs. CXCR4-tropic) in the absence of Vif.
- To identify specific cellular environments where HIV might evade APOBEC3-mediated restriction.
- To elucidate mechanisms of HIV escape and persistence despite APOBEC3 activity.
Main Methods:
- In vitro and in vivo experiments using vif-defective HIV strains.
- Analysis of APOBEC3 expression in thymocytes.
- Viral load monitoring and proviral DNA sequencing (G to A mutations) in various organs.
Main Results:
- APOBEC3 efficiently restricts CCR5-tropic HIV without Vif.
- CXCR4-tropic HIV escapes APOBEC3 restriction and replicates in vivo, particularly in thymocytes with low A3G/A3F expression.
- Vif-defective viruses showed extensive G to A mutations in other organs, indicating APOBEC3 activity, but replication persisted in the thymus.
Conclusions:
- Thymocytes represent a niche where HIV can circumvent APOBEC3 restriction in a Vif-independent manner.
- Despite Vif's role in HIV resistance, APOBEC3 significantly inactivates CCR5-tropic HIV.
- This study reveals specific cellular evasion strategies against innate antiviral factors.
