title: A virus-virus interaction circumvents the virus receptor requirement for infection by pathogenic retroviruses.
abstract: During ongoing C-type retrovirus infection, the probability of leukemia caused by insertional gene activation is markedly increased by the emergence of recombinant retroviruses that repeatedly infect host cells. The murine mink cell focus-inducing (MCF) viruses with this property have acquired characteristic changes in the N-terminal domain of their envelope glycoprotein that specify binding to a different receptor than the parental ecotropic virus. In this report, we show that MCF virus infection occurs through binding to this receptor (termed Syg1) and, remarkably, by a second mechanism that does not utilize the Syg1 receptor. By the latter route, the N-terminal domain of the ecotropic virus glycoprotein expressed on the cell surface in a complex with its receptor activates the fusion mechanism of the MCF virus in trans. The rate of MCF virus spread through a population of permissive human cells was increased by establishment of trans activation, indicating that Syg1 receptor-dependent and -independent pathways function in parallel. Also, trans activation shortened the interval between initial infection and onset of cell-cell fusion associated with repeated infection of the same cell. Our findings indicate that pathogenic retrovirus infection may be initiated by virus binding to cell receptors or to the virus envelope glycoprotein of other viruses expressed on the cell surface. Also, they support a broader principle: that cooperative virus-virus interactions, as well as virus-host interactions, shape the composition and properties of the retrovirus quasispecies.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Wensel
authors.forename: Weihua
authors.initials: W
authors.lastname: Li
authors.forename: James M
authors.initials: JM
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D006224:Cricetinae; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D008908:Mink Cell Focus-Inducing Viruses / Q000378:metabolism* / Q000472:pathogenicity*; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000089842:Xenotropic and Polytropic Retrovirus Receptor
chemical_list: D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor; C000715268:Xpr1 protein, mouse