Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection.
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.
Santiago
Mario L
ML
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
Montano
Mauricio
M
Benitez
Robert
R
Messer
Ronald J
RJ
Yonemoto
Wes
W
Chesebro
Bruce
B
Hasenkrug
Kim J
KJ
Greene
Warner C
WC
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000502:physiology; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014766:Viremia
D000914:Antibodies, Viral; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase
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