Unraveling how Rfv3/Apobec3 promotes the retrovirus-specific neutralizing antibody response (105.12)
| Autor: | Mario Santiago, Diana Smith, Bradley Barrett, Kejun Guo, Karl Heilman, Robert Benitez, Mauricio Montano, Roberta Pelanda, Kim Hasenkrug, Warner Greene |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:105.12-105.12 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Recovery from Friend retrovirus gene 3 (Rfv3) is a classical autosomal dominant gene that facilitates recovery from viremia and disease by promoting a more potent neutralizing antibody (NAb) response. We previously reported that Rfv3 is encoded by Apobec3, a deoxycytidine deaminase that can restrict a broad range of retroviruses. However, the mechanism for how Apobec3 promotes NAb responses and the nature of protective NAbs remain unclear. Apobec3 is related to Activation Induced Deaminase, but hapten-specific antibody affinity maturation is unaffected in Apobec3 deficient mice. In contrast, Apobec3 restriction of acute FV infection in immune cells is associated with more vigorous induction of germinal center B cells, increased B cell maturation and decreased hypergammaglobulinemia. Surprisingly, while Apobec3 reduced acute plasma infectious virus titers, plasma viral RNA loads were maintained. These plasma virions encounter an early reverse transcription block with minimum G-to-A mutations. Thus, Apobec3 appears to promote NAb responses by (1) reducing virus-induced immune dysfunction, while (2) facilitating substantial release of noninfectious viral particles, presumably to prime the B cell response. Finally, enhanced NAb responses in Rfv3/Apobec3 resistant mice correlated with virus-specific IgG1 and IgG3 titers. These findings highlight a fascinating interplay between innate Apobec3 restriction and humoral immunity, with potential implications for HIV vaccine development. |
| Databáze: | OpenAIRE |
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