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Journal of Virology, January 2009, p. 512-521, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01658-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Exosomes Packaging APOBEC3G Confer Human Immunodeficiency Virus Resistance to Recipient Cells{triangledown}

Atanu K. Khatua, Harry E. Taylor, James E. K. Hildreth, and Waldemar Popik*

Meharry Medical College, Center for AIDS Health Disparities Research, Nashville, Tennessee 37208

Received 4 August 2008/ Accepted 29 October 2008

The human cytidine deaminase APOBEC3G (A3G) is a part of a cellular defense system against human immunodeficiency virus type 1 (HIV-1) and other retroviruses. Antiretroviral activity of A3G can be severely blunted in the presence of the HIV-1 protein Vif. However, in some cells expressing the enzymatically active low-molecular-mass form of A3G, HIV-1 replication is restricted at preintegration steps, before accumulation of Vif. Here, we show that A3G can be secreted by cells in exosomes that confer resistance to both vif-defective and wild-type HIV-1 in exosome recipient cells. Our results also suggest that A3G is the major exosomal component responsible for the anti-HIV-1 activity of exosomes. However, enzymatic activity of encapsidated A3G does not correlate with the observed limited cytidine deamination in HIV-1 DNA, suggesting that A3G-laden exosomes restrict HIV-1 through a nonenzymatic mechanism. Real-time PCR quantitation demonstrated that A3G exosomes reduce accumulation of HIV-1 reverse transcription products and steady-state levels of HIV-1 Gag and Vif proteins. Our findings suggest that A3G exosomes could be developed into a novel class of anti-HIV-1 therapeutics.


* Corresponding author. Mailing address: Center for AIDS Health Disparities Research, Meharry Medical College, 1005 D. B. Todd Blvd., Nashville, TN 37208. Phone: (615) 327-6734. Fax: (615) 963-3146. E-mail: wpopik{at}mmc.edu

{triangledown} Published ahead of print on 5 November 2008.


Journal of Virology, January 2009, p. 512-521, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01658-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.