Role of infectious virus expression and immune response in retrovirus-induced oncogenesis.
Some of the parameters involved in retrovirus-induced oncogenesis were analyzed in newborn mice injected with Moloney-murine leukemia virus (M-MuLV) as well as in adults who received the virus by the intraperitoneal (i.p.) or intrathymic (i.t.) route. The neonatally injected mice were permissive for both viral replication and virus-induced cell-surface antigen expression on thymus cells, peripheral T and B lymphocytes, and macrophages, whereas the M-MuLV was not present in the adult i.p. injected mice. Instead, in i.t. injected mice, the virus was expressed in thymus and peripheral T cells only, but was not detected in tail extracts as assessed by means of the UV-XC plaque assay. Lack of virus spread in adult-treated animals correlated with a prompt humoral and cellular immune response, whereas the highly viremic newborn inoculated mice showed negligible virus-specific antibody production and an extremely low frequency of splenic cytotoxic T lymphocyte precursors. Moreover, immune response in both groups of adult-treated mice efficiently prevented tumor induction by Moloney-murine sarcoma virus (M-MuSV), which has the same antigenic determinants as M-MuLV, its natural helper. In contrast, M-MuSV sarcomas grew progressively in newborn inoculated mice and killed the host. Finally, 80% of neonatally injected mice developed lymphomas, whereas all treated adults remained free of disease for more than 15 months. These findings imply that the immune response may, in fact, prevent retrovirus-induced oncogenesis through restriction of virus replication and/or destruction of virus-infected cells.
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000954:Antigens, Surface / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D017988:Gammaretrovirus / Q000276:immunology*; D007114:Immunization; D007942:Leukemia, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012157:Mononuclear Phagocyte System / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology*; D014412:Tumor Virus Infections; D010948:Viral Plaque Assay; D014779:Virus Replication
D000954:Antigens, Surface; D000956:Antigens, Viral