Published 18 July 2005. doi:10.1083/jcb1702iti5
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 2, 163-163
Viruses catch a wave
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Virus (red) moves up filopodia before entering cells.
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Scientists know from looking at fixed cells that viruses frequently associate with filopodia and microvilli. Using video microscopy, Lehmann et al. (page 317) find that after a virus attaches to the filopodial membrane, it surfs down the plasma membrane toward the cell body. Entry into the cell occurs only after the virus has reached the base of the filopodium.
Retroviruses labeled with YFP initially contacted the filopodia of cells grown in culture. After a brief period of moving randomly on the filipodial surface, the viruses moved steadily in a retrograde fashion. Once the virus reached the cell body, the viral and host cell membranes fused, as detected by the diffusion of the fluorescently labeled envelope protein of the virus.
Vesicular stomatitis viruses, pH-dependent viruses that require endocytosis before membrane fusion, also surfed to the base of the filopodium, where they colocalized with clathrin.
Viral surfing did not occur in cells lacking the cognate viral receptor or those treated with cytochalasin D, but it was unaffected by nocodozole. Similarly, inhibition of myosin II with blebbistatin slowed viral movement and reduced infection by about fivefold.
The researchers hypothesize that viral entry only occurs at hot spots for endocytosis, which are concentrated at the base of the filopodia. And, they note, a similar observation was seen when quantum dots were used to label a ligand that binds to cell surface receptors (Lidke et al. 2004. Nat. Biotechnol. 22:198). Although the role of actin and myosin was not explored in that study, Lehmann et al. think that retrograde transport may be a common requirement for endocytosis of molecules or particles that initially bind on the filipodial surface. Moreover, the endocytic hot spots coincide with sites of actin remodeling, which may be necessary to allow signals to move rapidly through the otherwise highly structured ring of cortical actin. 
Rabiya S. Tuma
rabiya{at}nasw.org
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