Localization of HIV RNA in mitochondria of infected cells: potential role in cytopathogenicity.

• Type of Material: Article
• Authors: Mohan Somasundaran, University of Massachusetts; Maria L. Zapp, University of Massachusetts; Lars K. Beattie, University of Massachusetts; Lizhen Pang, University of Massachusetts; Kevin S. Byron, University of Massachusetts; Gary Bassell, Emory University; John L. Sullivan, University of Massachusetts; Robert H. Singer, University of Massachusetts
• Language: English
• Date: 1994-09-01
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © The Rockefeller University Press
• Final Published Version (URL): http://dx.doi.org/10.1083/jcb.126.6.1353
• Title of Journal or Parent Work: Journal of Cell Biology
• ISSN: 0021-9525
• Volume: 126
• Issue: 6
• Start Page: 1353
• End Page: 1360
• Keywords: Science & Technology; HTLV-III/LAV ENVELOPE; SURVIVAL; Life Sciences & Biomedicine; CELL BIOLOGY; HUMAN-IMMUNODEFICIENCY-VIRUS; INDUCTION; CONTAINS; MECHANISM; RAPID COLORIMETRIC ASSAY; DISEASE; INSITU HYBRIDIZATION; IMMUNE-DEFICIENCY SYNDROME; Cell Biology

Abstract

The intracellular distribution of HIV-1 RNA transcripts in infected cells was studied using in situ hybridization detected by electron microscopy and cellular fractionation. Although viral RNA and core protein could be detected throughout the cytoplasm and nucleus, viral RNA was found in significantly increased amounts in mitochondria relative to the cytoplasm and nucleus. In contrast, cellular poly(A) RNA or viral gag proteins were not increased in the mitochondria. A cell line containing an integrated latent genome that could be induced to express viral RNA after phorbol ester stimulation showed an increase in viral RNA accumulation in mitochondria parallel with the increase in HIV expression levels. Concomitant with HIV expression, there was a decrease in mitochondrial viability. Using immunofluorescent markers to detect probes to HIV RNA transcripts and antibodies to mitochondrial proteins simultaneously in single cells, there was an inverse relationship between the amount of viral RNA and mitochondrial integrity. High levels of viral RNA in mitochondria were found in acutely (but not chronically) infected cells. We propose that HIV RNA import into mitochondria can compromise mitochondrial function.