Student Author(s)

Serene Forte

UMMS Affiliation

Department of Pediatrics; Program in Molecular Medicine

Publication Date

1996-11-20

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences | Pediatrics

Abstract

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.

Rights and Permissions

This is a copy of an article published in AIDS Research and Human Retroviruses © 1996 Mary Ann Liebert, Inc.; AIDS Research and Human Retroviruses is available online at: http://www.liebertonline.com.

DOI of Published Version

10.1089/aid.1996.12.1585

Source

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

Journal/Book/Conference Title

AIDS research and human retroviruses

Related Resources

Link to article in PubMed

PubMed ID

8947293

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