Infection of Human Fetal Cardiac Myocytes by a Human Immunodeficiency Virus-1–Derived Vector

From the Department of Pediatrics, University of California Los Angeles School of Medicine, Los Angeles, Calif.

Correspondence to Michael A. Rebolledo, MD, UCLA Medical Center, Department of Pediatrics, Division of Cardiology, Box 951743, Room B2-427 MDCC, Los Angeles, CA 90095-1743. E-mail mrebolle{at}ucla.edu

Abstract—Cardiomyopathy associated with HIV-1 infection is a well-recognized complication. However, it is unknown whether direct cardiomyocyte infection is involved in the pathogenesis of the cardiomyopathy. An HIV-1–based lentiviral vector and wild-type HIV-1 were used to infect human fetal cardiac myocytes in a primary culture. Quantitative polymerase chain reaction, viral p24 antigen determination, and immunofluorescence were used to detect the synthesis of HIV-1 DNA and proteins after the infection. High-efficiency infection occurred using the HIV-1–based lentiviral vector, although no infection occurred with the wild-type HIV-1 strain. Dual-labeling immunofluorescence for HIV-1 proteins and myosin confirmed that cardiomyocytes were infected. This in vitro analysis suggests that direct myocyte infection with wild-type HIV-1 may not be involved in the pathogenesis of HIV-1 cardiomyopathy. However, HIV-1–based vectors may prove useful for ex vivo cardiovascular gene therapy.

Key Words: fetal heart • gene therapy • cardiomyopathy • human immunodeficiency virus • cell culture

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