Use of different but overlapping determinants in a retrovirus receptor accounts for non-reciprocal interference between xenotropic and polytropic murine leukemia viruses.
BACKGROUND
Retrovirus infection depends on binding of the retroviral envelope (Env) protein to specific cell-surface protein receptors. Interference, or superinfection resistance, is a frequent consequence of retroviral infection, and occurs when newly-synthesized Env binds to receptor proteins resulting in a block to entry by retroviruses that use the same receptors. Three groups of viruses demonstrate a non-reciprocal pattern of interference (NRI), which requires the existence of both a common receptor utilized by all viruses within the group, and a specific receptor that is used by a subset of viruses. In the case of amphotropic and 10A1 murine leukemia viruses (MLV), the common and specific receptors are the products of two related genes. In the case of avian sarcoma and leukosis virus types B, D, and E, the two receptors are distinct protein products of a single gene. NRI also occurs between xenotropic and polytropic MLV. The common receptor, Xpr1, has been identified, but a specific receptor has yet to be described.


RESULTS
Using chimeric receptor proteins and interference studies, we have identified a region of Xpr1 that is uniquely utilized by xenotropic MLV and show that this receptor domain is required for non-reciprocal interference.


CONCLUSIONS
We propose a novel pattern of receptor usage by xenotropic and polytropic MLV to explain the NRI observed between these viruses. We propose that the specific and common receptor determinants for xenotropic and polytropic viruses are simultaneously present in discreet domains of a single Xpr1 protein.
Van Hoeven
Neal S
NS
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. nvanhoeven@cdc.gov
Miller
A Dusty
AD
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009052:Leukemia Virus, Murine / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000378:metabolism / Q000472:pathogenicity*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014762:Viral Interference; D000089842:Xenotropic and Polytropic Retrovirus Receptor
D015686:Gene Products, env; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor; C000715268:Xpr1 protein, mouse