Persistent infection of mice by lactate dehydrogenase-elevating virus: effects of immunosuppression on virus replication and antiviral immune responses.
Maximum plasma titers (10(9)-10(10) ID50/ml) of lactate dehydrogenase-elevating virus (LDV) in mice are observed one day after infection, but then decrease 4-5 log during the next 5 weeks to attain a persistent steady-state level for the remainder of the life of the animal. The decrease in plasma LDV level during the first 5 weeks after infection and long-term viremia were not affected by lethal X-irradiation of the mice, daily injections of cyclosporin A or depletion of the mice of T cells by treatment with anti-CD4, anti-CD8, or anti-Thy1.2 monoclonal antibodies, although these treatments inhibited the formation of anti-LDV antibodies. LDV viremia was also the same in nu/nu and nu/+ Swiss mice, though the former did not mount an anti-LDV immune response, while the latter did. The appearance of anti-LDV neutralizing antibodies in infected mice 1-2 months after infection or the injection of infected mice with high doses of anti-LDV neutralizing monoclonal antibodies also did not affect the level of LDV viremia. Repeated treatments of infected mice with either cyclophosphamide or dexamethasone caused 1-2 log increases in plasma LDV titers. Although cyclophosphamide treatment prevented the formation of anti-LDV antibodies, dexamethasone caused an increase in plasma LDV levels without affecting anti-LDV antibody formation. We conclude that an anti-LDV immune response does not play a significant role in controlling LDV replication in mice. The data support the view that within 1 day after infection of a mouse, all LDV-permissive macrophages, which appear to be the only cells supporting LDV replication in the mouse, are destroyed as a result of a cytocidal infection by LDV. Subsequently, LDV replication is limited by the rate of generation of new permissive macrophages. The steady-state viremia attained about 5 weeks after infection reflects a balance between LDV replication in permissive macrophages as they arise and LDV inactivation and clearance.
Onyekaba
C O
CO
Department of Microbiology, Medical School University of Minnesota, Minneapolis 55455.
Harty
J T
JT
Even
C
C
Hu
B G
BG
Plagemann
P G
PG
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D005260:Female; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007772:Lactate dehydrogenase-elevating virus / Q000276:immunology* / Q000502:physiology; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology* / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects / Q000528:radiation effects
D000914:Antibodies, Viral; D007166:Immunosuppressive Agents