title: Foamy virus envelope glycoprotein-mediated entry involves a pH-dependent fusion process.
abstract: In general, enveloped viruses use two different entry strategies and are classified accordingly into pH-dependent and pH-independent viruses. Different members of the retrovirus family use one or the other strategy. Little is known about the uptake of foamy viruses (FV), a special group of retroviruses, into the target cells. In this study, we examined the pH dependence of FV entry by analyzing FV envelope glycoprotein (Env)-mediated infection of target cells with murine leukemia virus or FV vector pseudotypes in the presence of various lysosomotropic agents. Similar to vesicular stomatitis virus glycoprotein G (VSV-G)-mediated uptake, FV Env-mediated entry was inhibited by various lysosomotropic agents, suggesting a pH-dependent endocytic pathway. However, in contrast to its effect on VSV-G pseudotypes, chloroquine failed to reduce the infectivity of FV Env pseudotypes, implying that the pathway is different from that of VSV-G. Glycoproteins of various other FV species showed inhibition profiles similar to that of the prototype FV (PFV) Env. Analysis of the pH dependence of the FV Env-mediated fusion process in a cell-to-cell fusion assay revealed an induction of syncytium formation by a short exposure to acidic pH, peaking around pH 5.5. Interestingly, of all FV Env species analyzed, only the PFV Env had a significant fusion activity at neutral pH. Taken together, these data suggest a pH-dependent endocytic pathway for infection of target cells by FV.
authors.affiliation: Institut für Virologie und Immunbiologie, Universität Würzburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Picard-Maureau
authors.forename: Gergely
authors.initials: G
authors.lastname: Jarmy
authors.forename: Angelika
authors.initials: A
authors.lastname: Berg
authors.forename: Axel
authors.initials: A
authors.lastname: Rethwilm
authors.forename: Dirk
authors.initials: D
authors.lastname: Lindemann
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002459:Cell Fusion; D002460:Cell Line; D005822:Genetic Vectors; D015726:Giant Cells; D049452:Green Fluorescent Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018942:Macrolides; D008561:Membrane Fusion; D009550:Nigericin / Q000494:pharmacology; D016092:Spumavirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D008164:Luminescent Proteins; D018942:Macrolides; D014759:Viral Envelope Proteins; D000643:Ammonium Chloride; D049452:Green Fluorescent Proteins; C036978:concanamycin A; D009550:Nigericin