114 : Interferon-alpha therapy enhances the anti-friend virus B cell response through Apobec3

• Published in: Cytokine (Philadelphia, Pa.) Vol. 63; no. 3; p. 270
• Main Authors: Harper, Michael S., Barrett, Bradley S., Smith, Diana S., Heilman, Karl J., Li, Sam X., Dittmer, Ulf, Hasenkrug, Kim J., Santiago, Mario L.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.09.2013
• Subjects: clinical trials; cytokines; immunoglobulin G; interferon-alpha; mice; neutralizing antibodies; patients; Retroviridae; therapeutics; viral load; viruses
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2013.06.117

Therapeutic administration of IFN-α in clinical trials significantly reduced HIV-1 plasma viral load and HTLV-I proviral load in infected patients. However, the downstream antiretroviral effector(s) of IFN-α therapy remain unknown. Here we use the mouse Friend virus (FV) infection model to interrogate a potential effector protein, Apobec3. Lab and wild strains of mice have one of two forms of Apobec3, one associated with greater resistance to Friend Retrovirus (Rfv3r) and improved neutralizing antibody titers, and one associated with greater susceptibility (Rfv3s). We previously showed that in B6 mice, which are Rfv3r/r, IFN-α treatment inhibits acute FV infection primarily through Apobec3in vivo. This raised the question of whether IFN-therapy could be effective in an Rfv3s/s mouse strain. Additionally, we asked if IFN-treatment could therapeutically improve neutralizing antibody responses through Apobec3. Here we show that an IFN-α treatment regimen potently restricts acute FV in the Rfv3s/s 129 mouse strain independently of Apobec3, suggesting that different IFN-effectors may have evolutionarily gained potency in the absence of resistant Apobec3. However, IFN-α efficacy in later infection was dependent on Apobec3, and was associated with an increase in FV-reactive IgG2a. The increase in FV-reactive IgG2a was associated with an Apobec3-dependent B cell response characterized by increased germinal center and plasmablast formation. These data show that even the weak form of Apobec3 stimulates an enhanced B cell response during IFN-therapy, which confirms the potential of the IFN-Apobec3 axis as an antiretroviral therapeutic target or vaccine adjuvant.