This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Haché, G.
Right arrow Articles by Harris, R. S.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Haché, G.
Right arrow Articles by Harris, R. S.

 Previous Article  |  Next Article 

Journal of Virology, June 2009, p. 5956-5960, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00045-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Optimal Translation Initiation Enables Vif-Deficient Human Immunodeficiency Virus Type 1 To Escape Restriction by APOBEC3G{triangledown} ,{dagger}

Guylaine Haché,1,2,3 Truus E. M. Abbink,4 Ben Berkhout,5 and Reuben S. Harris1,2,3*

University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics,1 Institute for Molecular Virology,2 Center for Genome Engineering, Minneapolis, Minnesota 55455,3 University of Cambridge, Department of Medicine, Cambridge, United Kingdom,4 University of Amsterdam, Laboratory of Experimental Virology, Academic Medical Center, The Netherlands5

Received 8 January 2009/ Accepted 9 March 2009

APOBEC3G restricts Vif-deficient human immunodeficiency virus type 1 (HIV-1) by deaminating viral cDNA cytosines to uracils. This promutagenic activity is counteracted by HIV-1 Vif, which is a natural APOBEC3G antagonist. However, we previously reported that Vif-deficient HIV-1 could evolve resistance to APOBEC3G by a novel mechanism requiring an A200-to-C/T transition mutation and Vpr inactivation. A pyrimidine at nucleotide 200 in the untranslated leader region contributed to resistance by increasing virus particle production, which resulted in fewer APOBEC3G molecules per particle. Here we show that the A200-to-C/T mutation functions posttranscriptionally by inactivating an upstream start codon, which in turn enables optimal viral mRNA translation from canonical start codons.


* Corresponding author. Mailing address: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455. Phone: (612) 624-0457. Fax: (612) 625-2163. E-mail: rsh{at}umn.edu

{triangledown} Published ahead of print on 18 March 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.


Journal of Virology, June 2009, p. 5956-5960, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00045-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.