Mechanisms of avian retroviral host range extension.
Alpharetroviruses provide a useful system for the study of the molecular mechanisms of host range and receptor interaction. These viruses can be divided into subgroups based on diverse receptor usage due to variability within the two host range determining regions, hr1 and hr2, in their envelope glycoprotein SU (gp85). In previous work, our laboratory described selection from a subgroup B avian sarcoma-leukosis virus of an extended-host-range variant (LT/SI) with two adjacent amino acid substitutions in hr1. This virus retains its ability to use the subgroup BD receptor but can also infect QT6/BD cells, which bear a related subgroup E receptor (R. A. Taplitz and J. M. Coffin, J. Virol 71:7814-7819, 1997). Here, we report further analysis of this unusual variant. First, one (L154S) of the two substitutions is sufficient for host range extension, while the other (T155I) does not alter host range. Second, these mutations extend host range to non-avian cell types, including human, dog, cat, mouse, rat, and hamster. Third, interference experiments imply that the mutants interact efficiently with the subgroup BD receptor and possibly the related subgroup E receptor, but they have another means of entry that is not dependent on these interactions. Fourth, binding studies indicate that the mutant SU proteins retain the ability to interact as monomers with subgroup BD and BDE receptors but only bind the subgroup E receptor in the context of an Env trimer. Further, the mutant SU proteins bind well to chicken cells but do not bind any better than wild-type subgroup B to QT6 or human cells, even though the corresponding viruses are capable of infecting these cells.
Rainey
G Jonah A
GJ
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Natonson
Andrew
A
Maxfield
Lori F
LF
Coffin
John M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics / Q000472:pathogenicity*; D001358:Avian Sarcoma Viruses / Q000235:genetics / Q000472:pathogenicity*; D002415:Cats; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D006224:Cricetinae; D004285:Dogs; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D011991:Receptors, Virus / Q000378:metabolism*; D011995:Recombination, Genetic; D013045:Species Specificity; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D007074:Immunoglobulin G; D011991:Receptors, Virus; C062389:Rous sarcoma virus envelope protein gp85; D014759:Viral Envelope Proteins