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Journal of Virology, April 2003, p. 4722-4730, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4722-4730.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Foamy Virus Envelope Glycoprotein-Mediated Entry Involves a pH-Dependent Fusion Process

Marcus Picard-Maureau,1 Gergely Jarmy,1,{dagger} Angelika Berg,1 Axel Rethwilm,2 and Dirk Lindemann1,2*

Institut für Virologie und Immunbiologie, Universität Würzburg, Würzburg,1 Institut für Virologie, Medizinische Fakultät "Carl Gustav Carus," Technische Universität Dresden, Dresden, Germany2

Received 18 September 2002/ Accepted 16 January 2003

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.

* Corresponding author. Mailing address: Institut für Virologie, Medizinische Fakultät "Carl Gustav Carus," Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Phone: 49-351-458-6210. Fax: 49-351-458-6314. E-mail: dirk.lindemann{at}mailbox.tu-dresden.de.

{dagger} Present address: Universitätskinderklinik, Universität Ulm, Ulm, Germany.

Journal of Virology, April 2003, p. 4722-4730, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4722-4730.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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