Origin and rapid evolution of a novel murine erythroleukemia virus of the spleen focus-forming virus family.
The Friend spleen focus-forming virus (SFFV) env gene encodes a glycoprotein with apparent Mr of 55,000 that binds to erythropoietin receptors (EpoR) to stimulate erythroblastosis. A retroviral vector that does not encode any Env glycoprotein was packaged into retroviral particles and was coinjected into mice in the presence of a nonpathogenic helper virus. Although most mice remained healthy, one mouse developed splenomegaly and polycythemia at 67 days; the virus from this mouse reproducibly caused the same symptoms in secondary recipients by 2 to 3 weeks postinfection. This disease, which was characterized by extramedullary erythropoietin-independent erythropoiesis in the spleens and livers, was also reproduced in long-term bone marrow cultures. Viruses from the diseased primary mouse and from secondary recipients converted an erythropoietin-dependent cell line (BaF3/EpoR) into factor-independent derivatives but had no effect on the interleukin-3-dependent parental BaF3 cells. Most of these factor-independent cell clones contained a major Env-related glycoprotein with an Mr of 60,000. During further in vivo passaging, a virus that encodes an Mr-55,000 glycoprotein became predominant. Sequence analysis indicated that the ultimate virus is a new SFFV that encodes a glycoprotein of 410 amino acids with the hallmark features of classical gp55s. Our results suggest that SFFV-related viruses can form in mice by recombination of retroviruses with genomic and helper virus sequences and that these novel viruses then evolve to become increasingly pathogenic.
Hoatlin
M E
ME
Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health Sciences University, Portland 97201-3098, USA.
Gomez-Lucia
E
E
Lilly
F
F
Beckstead
J H
JH
Kabat
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral; D005260:Female; D004915:Leukemia, Erythroblastic, Acute / Q000662:veterinary* / Q000821:virology; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011086:Polycythemia / Q000821:virology; D017467:Receptors, Erythropoietin / Q000378:metabolism; D012192:Retroviridae Infections / Q000662:veterinary* / Q000821:virology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013155:Spleen Focus-Forming Viruses / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D013163:Splenomegaly / Q000821:virology; D014412:Tumor Virus Infections / Q000662:veterinary* / Q000821:virology
D004279:DNA, Viral; D017467:Receptors, Erythropoietin