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Updated: Jul 14, 2026
Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
Cardiac repolarization is prolonged in CD4C/HIV transgenic mice
Judith Brouillette1, Scott A Grandy, Paul Jolicoeur
1Research Center, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8.
Insights
Human immunodeficiency virus (HIV) infection delays cardiac repolarization in mice, independent of medications. This finding suggests HIV itself may cause heart rhythm abnormalities in patients.
Area of Science:
- Cardiology
- Virology
- Molecular Biology
Background:
- Pharmacological treatments for Acquired Immunodeficiency Syndrome (AIDS) can cause QT prolongation and delayed repolarization.
- Emerging evidence indicates delayed repolarization may occur without drug intervention.
- The direct impact of Human Immunodeficiency Virus (HIV) on ventricular repolarization remains uncharacterized.
Purpose of the Study:
- To investigate the effects of HIV on cardiac ventricular repolarization.
- To characterize repolarization changes in a mouse model of HIV disease.
- To determine if HIV infection alone causes delayed repolarization.
Main Methods:
- Utilized CD4C/HIV transgenic mice, which model human AIDS.
- Recorded electrocardiograms (ECG) in conscious mice.
- Employed patch-clamp techniques to analyze action potentials and potassium (K+) currents in ventricular myocytes.
- Conducted echocardiography to assess cardiac structure and function.
Main Results:
- CD4C/HIV mice exhibited significantly prolonged QT intervals and action potential durations compared to wild-type controls.
- A notable reduction in outward K+ currents was observed in HIV transgenic mice.
- Cardiac structure and function remained comparable between HIV transgenic and control mice, ruling out heart failure or hypertrophy as causes.
- Delayed repolarization occurred in the absence of pharmacological agents.
Conclusions:
- HIV infection in mice leads to delayed ventricular repolarization.
- This delay is associated with reduced K+ currents.
- The findings suggest HIV itself, not just its treatment, may be responsible for cardiac repolarization abnormalities.
Abstract:
Pharmacological agents used to treat patients with AIDS have been associated with QT prolongation and result in delayed repolarization. New evidence suggests that delayed repolarization can occur independently of pharmacological therapy. However, the effect of HIV on ventricular repolarization has not been investigated. Therefore, the objective of this study was to characterize cardiac repolarization in a mouse model of human HIV disease. All experiments were conducted on HIV transgenic mice (CD4C/HIV). These mice express the human HIV gene nef in cells of immune system and develop a severe AIDS-like disease that is similar to that observed in humans. ECG was recorded in conscious free moving mice and patch-clamp techniques were used to record action potentials and K+ current densities in single ventricular myocytes. Results showed that the QT interval and action potential duration were significantly prolonged in CD4C/HIV mice compared to wild-type littermates. This delay in repolarization was associated with a significant reduction in outward K+ currents. Echocardiography showed that cardiac structure and function were similar in CD4C/HIV and littermate control mice. This suggests that the changes in ventricular repolarization were not the result of heart failure or cardiac hypertrophy. Overall, this study shows that repolarization was delayed in CD4C/HIV mice and that this phenotype occurred in the absence of any pharmacological intervention. Thus, it appears that HIV may be responsible for the delayed ventricular repolarization phenotype observed in CD4C/HIV mice.
