Unique resistance of I/LnJ mice to a retrovirus is due to sustained interferon gamma-dependent production of virus-neutralizing antibodies.
Selection of immune escape variants impairs the ability of the immune system to sustain an efficient antiviral response and to control retroviral infections. Like other retroviruses, mouse mammary tumor virus (MMTV) is not efficiently eliminated by the immune system of susceptible mice. In contrast, MMTV-infected I/LnJ mice are capable of producing IgG2a virus-neutralizing antibodies, sustain this response throughout their life, and secrete antibody-coated virions into the milk, thereby preventing infection of their progeny. Antibodies were produced in response to several MMTV variants and were cross-reactive to them. Resistance to MMTV infection was recessive and was dependent on interferon (IFN)-gamma production, because I/LnJ mice with targeted deletion of the INF-gamma gene failed to produce any virus-neutralizing antibodies. These findings reveal a novel mechanism of resistance to retroviral infection that is based on a robust and sustained IFN-gamma-dependent humoral immune response.
Purdy
Alexandra
A
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Case
Laure
L
Duvall
Melody
M
Overstrom-Coleman
Max
M
Monnier
Nilah
N
Chervonsky
Alexander
A
Golovkina
Tatyana
T
D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000096:biosynthesis*; D003429:Cross Reactions; D005260:Female; D014644:Genetic Variation; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008321:Mammary Glands, Animal / Q000276:immunology / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008892:Milk / Q000821:virology; D009500:Neutralization Tests; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D018089:Superantigens / Q000235:genetics; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D018089:Superantigens; D007371:Interferon-gamma