Type I interferon signaling is required for the APOBEC3/Rfv3-dependent neutralizing antibody response but not innate retrovirus restriction

• Published in: Retrovirology Vol. 14; no. 1; p. 25
• Main Authors: Barrett, Bradley S, Harper, Michael S, Jones, Sean T, Guo, Kejun, Heilman, Karl J, Kedl, Ross M, Hasenkrug, Kim J, Santiago, Mario L
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.04.2017; BioMed Central; BMC
• Subjects: Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antibody response; Binding sites; Cytidine Deaminase - metabolism; Deaminase; Dehydrogenases; Evolution & development; Friend murine leukemia virus - immunology; Friend murine leukemia virus - physiology; Friend retrovirus; Genes; IFNAR; Immunoglobulins; Infections; Interferon; Interferon Type I - metabolism; Lactic acid; LDV; Leukemia; Mice, Knockout; Neutralizing antibody; Receptor, Interferon alpha-beta - deficiency; Retroviruses; Rodents; Short Report; Signal Transduction; Viral infections; Virus Replication; α-Interferon; Deaminase; Friend retrovirus; Neutralizing antibody; IFNAR; LDV
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/s12977-017-0349-2

APOBEC3/Rfv3 restricts acute Friend retrovirus (FV) infection and promotes virus-specific neutralizing antibody (NAb) responses. Classical Rfv3 studies utilized FV stocks containing lactate-dehydrogenase elevating virus (LDV), a potent type I interferon inducer. Previously, we showed that APOBEC3 is required for the anti-FV activity of exogenous IFN-alpha treatment. Thus, type I interferon receptor (IFNAR) signaling may be required for the APOBEC3/Rfv3 response. To test if the APOBEC3/Rfv3 response is dependent on type I IFN signaling, we infected IFNAR knockout versus IFNAR/APOBEC3 double-knockout mice with FV/LDV or LDV-free FV, and evaluated acute FV infection and subsequent NAb titers. We show that LDV co-infection and type I IFN signaling are not required for innate APOBEC3-mediated restriction. By contrast, removal of LDV and/or type I IFN signaling abrogated the APOBEC3-dependent NAb response. APOBEC3 can restrict retroviruses in a type I IFN-independent manner in vivo. By contrast, the ability of APOBEC3 to promote NAb responses is type I IFN-dependent. These findings reveal novel insights on the interplay between type I IFNs and APOBEC3 in vivo that may have implications for augmenting antiretroviral NAb responses.