Up-regulation of the ubiquitin-conjugating and proteolytic systems in murine acquired immunodeficiency syndrome.
Lymphoproliferation, chronic B-cell activation resulting in hypergammaglobulinemia, and profound immunodeficiency are prominent features of retrovirus-induced murine acquired immunodeficiency syndrome (murine AIDS). Here we demonstrate that in murine AIDS the ATP-dependent and ubiquitin-dependent proteolytic system is strongly affected, at least in the lymph nodes of infected mice. Solid-phase immunochemical assays show that the ubiquitin-conjugate pools increase by about threefold 10 weeks after infection, then decline slightly 15 weeks after infection to a twofold increase. Accumulation of ubiquitin conjugates is accompanied by induction of the ubiquitin-conjugating pathway, involving several carrier-protein isozymes (E2), mainly 14-kDa E2 and 17-kDa E2. Furthermore, accumulation of ubiquitin conjugates and induction of the conjugating system are coincident with an increase in the proteolytic activity supported by the 26S proteolytic complex. However, 15 weeks after infection, when the conjugation rate and levels of ubiquitin conjugates decrease, proteasome activity returns to values similar to those of the control, suggesting that a higher proteosomal activity is no longer needed. The concerted induction of the ubiquitin-conjugating and proteolytic systems in murine AIDS apparently does not involve the breakdown of viral products nor is it supported by virus-coded events, but probably arises as a cellular response to viral infection.
Crinelli
R
R
Institute of Biological Chemistry, G. Fornaini, University of Urbino, Italy.
Fraternale
A
A
Casabianca
A
A
Magnani
M
M
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D008025:Ligases; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*; D015854:Up-Regulation
D002352:Carrier Proteins; D014452:Ubiquitins; C046288:ubiquitin carrier proteins; D000255:Adenosine Triphosphate; D044763:Ubiquitin-Conjugating Enzymes; D010450:Endopeptidases; D008025:Ligases