TY - JOUR
T1 - Origin and rapid evolution of a novel murine erythroleukemia virus of the spleen focus-forming virus family
AU - Hoatlin, Maureen E.
AU - Gomez-Lucia, Esperanza
AU - Lilly, Frank
AU - Beckstead, Jay H.
AU - Kabat, David
PY - 1998/5
Y1 - 1998/5
N2 - The Friend spleen focus-forming virus (SFFV) env gene encodes a glycoprotein with apparent M(r) 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 M(r) of 60,000. During further in vivo passaging, a virus that encodes an M(r)-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.
AB - The Friend spleen focus-forming virus (SFFV) env gene encodes a glycoprotein with apparent M(r) 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 M(r) of 60,000. During further in vivo passaging, a virus that encodes an M(r)-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.
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U2 - 10.1128/jvi.72.5.3602-3609.1998
DO - 10.1128/jvi.72.5.3602-3609.1998
M3 - Article
C2 - 9557641
AN - SCOPUS:0031978535
SN - 0022-538X
VL - 72
SP - 3602
EP - 3609
JO - Journal of virology
JF - Journal of virology
IS - 5
ER -