U3 long terminal repeat-mediated induction of intracellular immunity by a murine retrovirus: a novel model of latency for retroviruses.
BL/VL3 radiation leukemia virus (RadLV) is a thymotropic, highly leukemogenic murine leukemia virus (MuLV) which is unable to replicate in vitro in mouse fibroblasts. We have previously reported that the U3 long terminal repeat region of its genome is responsible for this block (E. Rassart, Y. Paquette, and P. Jolicoeur, J. Virol. 62:3840-3848, 1988). By using hybrids of permissive and resistant cells infected with BL/VL3 RadLV or fibrotropic MuLV, we found that the resistant phenotype was dominant. Investigation to determine at which step of the virus cycle the block operates revealed that integration, transcription, and translation of the BL/VL3 viral genome occurred at normal levels in nonpermissive cells. The BL/VL3 RadLV Pr65gag proteins made in nonpermissive cells were also myristylated and located at the membrane, and the levels of their cleaved products were similar to those of fibrotropic MuLV. However, processing of BL/VL3 RadLV Pr85env was impaired in nonpermissive cells. Virions were not released into the culture medium of nonpermissive cells, as measured by reverse transcriptase activity and by content in p30 or gp70 protein and as documented by lower levels of budding particles seen by electron microscopy. These results indicate that BL/VL3 RadLV replication is blocked at a late stage of the virus cycle, i.e., at virion assembly. Interestingly, these BL/VL3 RadLV-infected nonpermissive fibroblasts were resistant to superinfection by fibrotropic Moloney MuLV, and this resistance also occurred at a late step of the Moloney virus cycle. Since this block is dominant, it appears that the U3 long terminal repeat region of the BL/VL3 viral genome has the ability to induce a cellular suppressor factor(s), thus bringing intracellular immunity against itself and against other ecotropic MuLVs.
Gorska-Flipot
I
I
Laboratory of Molecular Biology, Clinical Research Institute of Montréal, Québec, Canada.
Huang
M
M
Cantin
M
M
Rassart
E
E
Massé
G
G
Jolicoeur
P
P
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells; D004247:DNA / Q000032:analysis / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D007111:Immunity, Cellular; D051379:Mice; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D011533:Proviruses / Q000235:genetics / Q000276:immunology; D016721:Radiation Leukemia Virus / Q000235:genetics* / Q000276:immunology*; D012091:Repetitive Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes; D014162:Transfection; D016662:Virus Integration
D004279:DNA, Viral; D015683:Gene Products, gag; D009227:Myristic Acids; D019814:Myristic Acid; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase