Abnormal regulation of IFN-alpha, -beta, and -gamma expression in MAIDS, a murine retrovirus-induced immunodeficiency syndrome.
Mice infected with LP-BM5 murine leukemia viruses (MuLV) develop a syndrome with many features in common with AIDS including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. To evaluate cellular defects that may predispose infected mice to these sequelae, we studied the regulation of IFN gene expression. Spleen cells from mice infected with LP-BM5 MuLV expressed high levels of IFN-gamma mRNA by 1 wk post-inoculation and throughout the course of disease. By comparison, transcripts of IFN-alpha/beta genes were not detected in spleen cells at any time after infection. In uninfected mice, expression of IFN-alpha/beta genes is induced rapidly after infection with New-castle disease virus, but mice inoculated with LP-BM5 MuLV were unable to induce these genes by 4 wk after retroviral infection. Inhibition of IFN-alpha/beta induction due to LP-BM5 MuLV infection also occurred in nude mice, indicating this effect was not mediated by activated T cells. Furthermore, low levels of IFN-gamma transcripts were detected in spleens of nude infected mice, suggesting that cells other than T cells can express this gene. These results suggest that the normal contributions of IFN to control of microbial spread, immune surveillance, and lymphoid interactions are disrupted by infection with LP-BM5 MuLV.
Pitha
P M
PM
Johns Hopkins University Oncology Center, Baltimore, MD 21205.
Biegel
D
D
Yetter
R A
RA
Morse
H C
HC
D000818:Animals; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D007370:Interferon Type I / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008908:Mink Cell Focus-Inducing Viruses; D012333:RNA, Messenger / Q000302:isolation & purification; D012192:Retroviridae Infections / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
D007370:Interferon Type I; D012333:RNA, Messenger; D007371:Interferon-gamma