Molecular and cellular basis of the retrovirus resistance in I/LnJ mice.

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Animals, Antibodies-Viral, Bone-Marrow-Cells, CD4-Positive-T-Lymphocytes, Enzyme-Linked-Immunosorbent-Assay, Flow-Cytometry, Immunity-Natural, Immunoglobulin-Fab-Fragments, Immunoglobulin-G, Interferon-Type-II, Mammary-Tumor-Virus-Mouse, Mice-Knockout, Microscopy-Electron-Transmission, Tumor-Virus-Infections, Virion

JAX Source

J Immunol 2005 Dec; 175(11):7543-9.


Previously, we showed that IFN-gamma elicited by mouse mammary tumor virus (MMTV) infection in I/LnJ mice stimulated production of virus-neutralizing Abs, mostly of the IgG2a isotype. These Abs coated virions secreted by infected I/LnJ cells, and thus completely prevented virus transmission to offspring. However, the mechanism of virus neutralization by isotype-specific Abs remained unknown. Ab coating is capable of blocking virus infection by interfering with receptor-virus binding, by virus opsonization, by complement activation, and via FcgammaR-mediated effector mechanisms. The aim of the studies described in this work was to uncover the cellular basis of anti-virus Ab production, to evaluate the importance of the IgG2a subclass of IgGs in virus neutralization, and to investigate which of the blocking mechanisms plays a role in virus neutralization. We showed that I/LnJ-derived bone marrow cells, specifically IFN-gamma-producing CD4+ T cells, were key cells conferring resistance to MMTV infection in susceptible mice upon transfer. We also established that a unique bias in the subclass selection toward the IgG2a isotype in infected I/LnJ mice was not due to their potent neutralizing ability, as anti-virus Abs of other isotypes were also able to neutralize the virus, but were a product of virally induced IFN-gamma. Finally, we demonstrated that F(ab')2 of anti-MMTV IgGs neutralized the virus as efficiently as total IgGs, suggesting that Ab-mediated interference with viral entry is the sole factor inhibiting virus replication in I/LnJ mice. We propose and discuss possible mechanisms by which infected I/LnJ mice eradicate retrovirus.