Temporal effects of gamma interferon deficiency on the course of Friend retrovirus infection in mice.
The current studies demonstrate complex and seemingly contradictory effects by gamma interferon (IFN-gamma) on Friend virus (FV) infection. Both temporal and tissue-specific effects were observed. During the first week of infection, IFN-gamma-deficiency caused increased levels of FV infection in multiple tissues. Surprisingly, however, by 2 weeks postinfection, IFN-gamma-deficient mice had significantly lower levels of infection in both the spleen and bone marrow compared to wild-type mice. The rapid reduction of virus in the IFN-gamma-deficient mice correlated with a more rapid virus-neutralizing antibody response than was observed in the wild-type mice. Furthermore, the virus-neutralizing antibody response in wild-type mice could be accelerated by ablation of their IFN-gamma response. Although the IFN-gamma-deficient mice developed an accelerated virus-neutralizing antibody response, they did not class-switch to immunoglobulin G class immunoglobulins nor could they maintain long-term virus-neutralizing antibody titers. Eventually, all of the IFN-gamma-deficient mice failed to keep persistent virus in check and developed fatal FV-induced erythroleukemia.
Stromnes
Ingunn M
IM
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases/NIH, Hamilton, Montana 59840, USA.
Dittmer
Ulf
U
Schumacher
Ton N M
TN
Schepers
Koen
K
Messer
Ronald J
RJ
Evans
Leonard H
LH
Peterson
Karin E
KE
Race
Brent
B
Hasenkrug
Kim J
KJ
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D005434:Flow Cytometry; D005622:Friend murine leukemia virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000821:virology; D007942:Leukemia, Experimental / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012192:Retroviridae Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D013154:Spleen / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology
D000914:Antibodies, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D011994:Recombinant Proteins; D007371:Interferon-gamma