Reports

Apobec3 Encodes Rfv3, a Gene Influencing Neutralizing Antibody Control of Retrovirus Infection

Mario L. Santiago,¹ Mauricio Montano,^1* Robert Benitez,^1* Ronald J. Messer,² Wes Yonemoto,¹ Bruce Chesebro,² Kim J. Hasenkrug,² Warner C. Greene^1,3,4

Recovery from Friend virus 3 (Rfv3) is a single autosomal gene encoding a resistance trait that influences retroviral neutralizing antibody responses and viremia. Despite extensive research for 30 years, the molecular identity of Rfv3 has remained elusive. Here, we demonstrate that Rfv3 is encoded by Apobec3. Apobec3 maps to the same chromosome region as Rfv3 and has broad inhibitory activity against retroviruses, including HIV. Not only did genetic inactivation of Apobec3 convert Rfv3-resistant mice to a susceptible phenotype, but Apobec3 was also found to be naturally disabled by aberrant messenger RNA splicing in Rfv3-susceptible strains. The link between Apobec3 and neutralizing antibody responses highlights an Apobec3-dependent mechanism of host protection that might extend to HIV and other human retroviral infections.

¹ Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
² Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA.
³ Department of Medicine, University of California, San Francisco, CA 94143–1230, USA.
⁴ Department of Microbiology and Immunology, University of California, San Francisco, CA 94143–1230, USA.

^* These authors contributed equally to this work.

To whom correspondence should be addressed. E-mail: khasenkrug{at}nih.gov (K.J.H.); wgreene{at}gladstone.ucsf.edu (W.C.G.)

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Effects of Acute and Chronic Murine Norovirus Infections on Immune Responses and Recovery from Friend Retrovirus Infection.

C. G. Ammann, R. J. Messer, K. Varvel, B. L. DeBuysscher, R. A. LaCasse, A. K. Pinto, and K. J. Hasenkrug (2009)
J. Virol. 83, 13037-13041
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The AKV Murine Leukemia Virus Is Restricted and Hypermutated by Mouse APOBEC3.

M.-A. Langlois, K. Kemmerich, C. Rada, and M. S. Neuberger (2009)
J. Virol. 83, 11550-11559
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Race between Retroviral Spread and CD4+ T-Cell Response Determines the Outcome of Acute Friend Virus Infection.

R. Pike, A. Filby, M. J.-Y. Ploquin, U. Eksmond, R. Marques, I. Antunes, K. Hasenkrug, and G. Kassiotis (2009)
J. Virol. 83, 11211-11222
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Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases.

J. Zielonka, I. G. Bravo, D. Marino, E. Conrad, M. Perkovic, M. Battenberg, K. Cichutek, and C. Munk (2009)
J. Virol. 83, 7547-7559
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Genetic Variants and Prostate Cancer Risk: Candidate Replication and Exploration of Viral Restriction Genes.

J. P. Breyer, K. M. McReynolds, B. L. Yaspan, K. M. Bradley, W. D. Dupont, and J. R. Smith (2009)
Cancer Epidemiol. Biomarkers Prev. 18, 2137-2144
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Expression of Murine APOBEC3 Alleles in Different Mouse Strains and Their Effect on Mouse Mammary Tumor Virus Infection.

C. M. Okeoma, J. Petersen, and S. R. Ross (2009)
J. Virol. 83, 3029-3038
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Powerful mutators lurking in the genome.

V. Petit, J.-P. Vartanian, and S. Wain-Hobson (2009)
Phil Trans R Soc B 364, 705-715
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Guidelines for Naming Nonprimate APOBEC3 Genes and Proteins.

R. S. LaRue, V. Andresdottir, Y. Blanchard, S. G. Conticello, D. Derse, M. Emerman, W. C. Greene, S. R. Jonsson, N. R. Landau, M. Lochelt, et al. (2009)
J. Virol. 83, 494-497
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