Immunology & Virology Program
Department of Pediatrics; Program in Molecular Medicine
Medical Subject Headings
CD4-Positive T-Lymphocytes; Cell Line; Cells, Cultured; Child, Preschool; Cytopathogenic Effect, Viral; Giant Cells; HIV Seropositivity; HIV-1; Humans; Leukocytes, Mononuclear; Mitochondria; Phenotype
Life Sciences | Medicine and Health Sciences | Pediatrics
To investigate the mechanisms of HIV-1 cytopathogenicity, functional biological HIV-1 clones were isolated from two infected children with high viral loads in vivo. Clone HC4 was isolated from a symptomatic child and clone GC6 8-4 was isolated from an asymptomatic child. These clones were characterized for their ability to induce syncytia, and to replicate and induce single-cell death in peripheral blood-derived normal CD4 T cell cultures containing anti-CD4 antibody. Despite similar viral loads as determined by p24 antigen production or viral RNA expression, GC6 8-4 was noncytopathogenic and HC4 was cytopathogenic. Since we had demonstrated that mitochondrial dysfunction correlated with HIV-1-induced cell death, we determined whether the cytopathogenic HC4 clone decreased mitochondrial viability using a mitochondrial-specific dye, rhodamine-123. Following infection, mitochondrial viability decreased in cells infected with HC4 by day 4 and continued to decline through day 7 when compared to uninfected cells. By day 7 postinfection, greater than 80% of the cells in culture were dead. Similar analyses on CD4 T cells infected with the noncytopathogenic GC6 8-4 demonstrated that mitochondria remained functionally viable and > 90% of the cells excluded trypan blue. These studies describe a cell culture system to study single-cell death in the absence of syncytia and secondary infection. Results with two patient-derived HIV-1 biological clones suggest that loss of mitochondrial viability may play a role in HIV-1-induced cytopathogenicity.
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Citation: AIDS Res Hum Retroviruses. 1996 Nov 20;12(17):1585-93. doi:10.1089/aid.1996.12.1585. Link to article on publisher's website