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Journal of Virology, September 2009, p. 9474-9485, Vol. 83, No. 18
0022-538X/09/$08.00+0 doi:10.1128/JVI.01089-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets
,
Fransje A. Koning,1
Edmund N. C. Newman,1,
Eun-Young Kim,2
Kevin J. Kunstman,2
Steven M. Wolinsky,2* and
Michael H. Malim1*
Department of Infectious Diseases, King's College London School of Medicine, London SE1 9RT, United Kingdom,1 Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611-28262
Received 28 May 2009/ Accepted 26 June 2009
Human APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we report a detailed examination of human APOBEC3 gene expression, focusing on APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif. A3G and A3F are expressed widely in hematopoietic cell populations, including T cells, B cells, and myeloid cells, as well as in tissues where mRNA levels broadly correlate with the lymphoid cell content (gonadal tissues are exceptions). By measuring mRNA copy numbers, we find that A3G mRNA is 
10-fold more abundant than A3F mRNA, implying that A3G is the more significant anti-HIV-1 factor in vivo. A3G and A3F levels also vary between donors, and these differences are sustained over 12 months. Responses to T-cell activation or cytokines reveal that A3G and A3F mRNA levels are induced 10-fold in macrophages and dendritic cells (DCs) by alpha interferon (IFN-
) and 4-fold in naïve CD4+ T cells. However, immunoblotting revealed that A3G protein levels are induced by IFN- in macrophages and DCs but not in T cells. In contrast, T-cell activation and IFN-
had a minimal impact on A3G or A3F expression. Finally, we noted that A3A mRNA expression and protein expression are exquisitely sensitive to IFN- induction in CD4+ T cells, macrophages, and DCs but not to T-cell activation or other cytokines. Given that A3A does not affect HIV-1 infection, these observations imply that this protein may participate in early antiviral innate immune responses.
* Corresponding author. Mailing address for Michael H. Malim: Department of Infectious Diseases, King's College London School of Medicine, 2nd Floor, Borough Wing, Guy's Hospital, London Bridge, London SE1 9RT, United Kingdom. Phone: 44 20 7188 0149. Fax: 44 20 7188 0147. E-mail: michael.malim{at}kcl.ac.uk. Mailing address for Steven M. Wolinsky: Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611. Phone: (312) 695-5067. Fax: (312) 695-5088. E-mail: s-wolinsky{at}northwestern.edu
Published ahead of print on 8 July 2009.
Supplemental material for this article may be found at http://jvi.asm.org/.
Present address: Centre for Emergency Preparedness and Response, Health Protection Agency, Porton Down, Wiltshire, United Kingdom.
Journal of Virology, September 2009, p. 9474-9485, Vol. 83, No. 18
0022-538X/09/$08.00+0 doi:10.1128/JVI.01089-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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