Noncytotoxic suppression of human immunodeficiency virus type 1 transcription by exosomes secreted from CD8+ T cells.

Abstract

CD8(+) T cells display a noncytotoxic activity that suppresses transcription of human immunodeficiency virus type 1 (HIV-1) in an antigen-independent and major histocompatibility complex-unrestricted manner. To date, the precise cellular and molecular factors mediating this CD8(+) T-cell effector function remain unsolved. Despite evidence indicating the dependence of the activity on cell-cell contact, the possibility of a membrane-mediated activity that represses transcription from the viral promoter remains unexplored. We therefore investigated whether this inhibition of HIV-1 transcription might be elicited by a membrane-bound determinant. Using a CD8(+) T-cell line displaying potent noncytotoxic HIV-1 suppression activity, we have identified a membrane-localized HIV-1-suppressing activity that is concomitantly secreted as 30- to 100-nm endosome-derived tetraspanin-rich vesicles known as exosomes. Purified exosomes from CD8(+) T-cell culture supernatant noncytotoxically suppressed CCR5-tropic (R5) and CXCR4-tropic (X4) replication of HIV-1 in vitro through a protein moiety. Similar antiviral activity was also found in exosomes isolated from two HIV-1-infected subjects. The antiviral exosomes specifically inhibited HIV-1 transcription in both acute and chronic models of infection. Our results, for the first time, indicate the existence of an antiviral membrane-bound factor consistent with the hallmarks defining noncytotoxic CD8(+) T-cell suppression of HIV-1.

• Authors: Ashwin Tumne, Varsha Shridhar Prasad, Yue Chen, Donna B Stolz, Kunal Saha, Deena M Ratner, Ming Ding, Simon C Watkins, Phalguni Gupta
• Journal: Journal of virology (J Virol) Vol. 83 Issue 9 Pg. 4354-64 (May 2009) ISSN: 1098-5514 [Electronic] United States
• PMID: 19193788 (Publication Type: Journal Article)

Chemical References

• STAT1 Transcription Factor

Topics

• CD8-Positive T-Lymphocytes (immunology, metabolism, ultrastructure)
• Cell Line
• Cell Membrane (immunology)
• Exosomes (immunology, metabolism)
• HIV-1 (genetics, immunology, metabolism, ultrastructure)
• Humans
• Microscopy, Electron, Transmission
• Promoter Regions, Genetic (genetics)
• STAT1 Transcription Factor (metabolism)
• Transcription, Genetic (genetics)
• Virus Replication