Subversion of the innate immune system by a retrovirus.
Retroviruses evolve rapidly to avoid the immune response of the infected host. We show here that the wild-type mouse mammary tumor virus MMTV(C3H) persisted indefinitely in C3H/HeN mice. However, it was rapidly lost in mice of the closely related C3H/HeJ strain and was replaced by a virus recombinant with an endogenous Mtv provirus. Maintenance of the wild-type virus was dependent on Toll-like receptor-4 (TLR4) signaling, which triggered production of the immunosuppressive cytokine interleukin-10. In the presence of mutant TLR4 in C3H/HeJ mice, wild-type virus was eliminated by the cytotoxic immune response, promoting selection of the immune escape recombinant MMTV variants. Thus, subversion of the innate immune system is yet another survival strategy used by retroviruses.
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Brooke A
BA
Jude
Yelena
Y
Pobezinskaya
Jennifer
J
Bishop
Susannah
S
Parke
Ruslan M
RM
Medzhitov
Alexander V
AV
Chervonsky
Tatyana V
TV
Golovkina
D000818:Animals; D003433:Crosses, Genetic; D003601:Cytotoxicity Tests, Immunologic; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000276:immunology; D011994:Recombinant Proteins; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology*; D012641:Selection, Genetic; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology*
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D016753:Interleukin-10