Analysis of the unique hamster cell tropism of ecotropic murine leukemia virus PVC-211.
PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV). Previous studies from our laboratory demonstrated that unlike the parental F-MuLV, PVC-211 MuLV can infect rat brain capillary endothelial cells efficiently and that it has acquired genetic changes responsible for its expanded cellular tropism. To determine if PVC-211 MuLV also has expanded its host range, we tested its infectivity on Chinese hamster ovary-derived CHO-K1 cells, which are generally resistant to ecotropic MuLV. The results indicated that PVC-211 MuLV, but not F-MuLV, was highly infectious for CHO-K1 cells. Studies using glycosylation inhibitors and glycosylation mutants of CHO-K1 cells, as well as interference studies, suggested that PVC-211 MuLV has acquired the ability to interact with the ecotropic MuLV receptor on CHO-K1 cells that has undergone glycosylation-dependent modification. Using chimeric viruses between PVC-211 MuLV and F-MuLV, we were able to localize the viral genetic element crucial for CHO-K1 cell tropism within the env gene of PVC-211 MuLV and show that glycine at position 116 and lysine at position 129 of the envelope glycoprotein SU were important. These viral determinants also appear to confer tropism for other hamster cells resistant to ordinary ecotropic MuLVs. Further studies on the interaction between PVC-211 MuLV and the receptor on hamster cells may provide novel insights into the molecular mechanisms for receptor recognition and binding by viral envelope glycoproteins.
Masuda
M
M
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Masuda
M
M
Hanson
C A
CA
Hoffman
P M
PM
Ruscetti
S K
SK
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004279:DNA, Viral; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005622:Friend murine leukemia virus / Q000235:genetics / Q000378:metabolism*; D015686:Gene Products, env / Q000235:genetics; D006031:Glycosylation / Q000187:drug effects; D017989:Leukemia Virus, Gibbon Ape / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D011991:Receptors, Virus / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
D004279:DNA, Viral; D015686:Gene Products, env; D011991:Receptors, Virus; D014415:Tunicamycin; D003847:Deoxyglucose; C099067:DNA modification methylase AgeI; D015257:DNA-Cytosine Methylases; C074326:CTTAAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific