Genetic regulation of long-term nonprogression in E-55+ murine leukemia virus infection in mice.
Certain inbred mouse strains display progression to lymphoma development after infection with E-55+ murine leukemia virus (E-55+ MuLV), while others demonstrate long-term nonprogression. This difference in disease progression occurs despite the fact that E-55+ MuLV causes persistent infection in both immunocompetent BALB/c-H-2(k) (BALB.K) progressor (P) and C57BL/10-H-2(k) (B10.BR) long-term nonprogressor (LTNP) mice. In contrast to immunocompetent mice, immunosuppressed mice from both P and LTNP strains develop lymphomas about 2 months after infection, indicating that the LTNP phenotype is determined by the immune response of the infected mouse. In this study, we used bone marrow chimeras to demonstrate that the LTNP phenotype is associated with the genotype of donor bone marrow and not the recipient microenvironment. In addition, we have mapped a genetic locus that may be responsible for the LTNP trait. Microsatellite-based linkage analysis demonstrated that a non-major histocompatibility complex gene on chromosome 15 regulates long-term survival and is located in the same region as the Rfv3 gene. Rfv3 is involved in recovery from Friend virus-induced leukemia and has been demonstrated to regulate neutralizing virus antibody titers. In our studies, however, both P and LTNP strains produce similar titers of neutralizing and cytotoxic anti-E-55+ MuLV. Therefore, while it is possible that Rfv3 influences the course of E-55+ MuLV infection, it is more likely that the LTNP phenotype in E-55+ MuLV-infected mice is regulated by a different, closely linked gene.
Panoutsakopoulou
V
V
Department of Pathology, MCP Hahnemann School of Medicine, Philadelphia, Pennsylvania 19102, USA.
Hunter
K
K
Sieck
T G
TG
Blankenhorn
E P
EP
Blank
K J
KJ
D000818:Animals; D001854:Bone Marrow Cells; D018450:Disease Progression; D004198:Disease Susceptibility; D008040:Genetic Linkage; D007113:Immunity, Innate; D007178:Inbreeding; D009052:Leukemia Virus, Murine / Q000276:immunology*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012192:Retroviridae Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology