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

• Published in: Science (American Association for the Advancement of Science) Vol. 321; no. 5894; pp. 1343 - 1346
• Main Authors: Santiago, Mario L, Montano, Mauricio, Benitez, Robert, Messer, Ronald J, Yonemoto, Wes, Chesebro, Bruce, Hasenkrug, Kim J, Greene, Warner C
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 05.09.2008; The American Association for the Advancement of Science
• Subjects: Animals; Antibodies; Antibodies, Viral - biosynthesis; Antibodies, Viral - blood; Antibodies, Viral - immunology; Biological and medical sciences; Chromosome Mapping; Chromosomes; Cloning, Molecular; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Exons; Friend murine leukemia virus - immunology; Friend murine leukemia virus - physiology; Fundamental and applied biological sciences. Psychology; Genes; Genetics; Human immunodeficiency virus; Immunity, Innate; Infections; Messenger RNA; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Molecular Sequence Data; Neutralization Tests; Neutralizing antibodies; Phenotypes; Proteins; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Retroviridae Infections - genetics; Retroviridae Infections - immunology; Retroviridae Infections - virology; Rodents; Tumor Virus Infections - genetics; Tumor Virus Infections - immunology; Tumor Virus Infections - virology; Viremia; Virology; Viruses; Immune response; Rodentia; Retroviridae; Neutralizing antibody; Infection; Virus; Vertebrata; Gammaretrovirus; Mammalia; Sensitivity resistance; Mouse; Viral disease; Friend murine leukemia virus; Humoral immunity
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1161121

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.