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Journal of Virology, August 2007, p. 8613-8620, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.00606-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Two Distinct Low-pH Steps Promote Entry of Vaccinia Virus{triangledown}

Alan C. Townsley and Bernard Moss*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Received 21 March 2007/ Accepted 29 May 2007

Entry of vaccinia virus into cells occurs by an endosomal route as well as through the plasma membrane. Evidence for an endosomal pathway was based on findings that treatment at a pH of <6 of mature virions attached to the plasma membrane enhances entry, whereas inhibitors of endosomal acidification reduce entry. Inactivation of infectivity by low-pH treatment of virions prior to membrane attachment is characteristic of many viruses that use the endosomal route. Nevertheless, we show here that the exposure of unattached vaccinia virus virions to low pH at 37°C did not alter their infectivity. Instead, such treatment stably activated virions as indicated by their accelerated entry upon subsequent addition to cells, as measured by reporter gene expression. Moreover, the rate of entry was not further enhanced by a second low-pH treatment following adsorption to the plasma membrane. However, the entry of virions activated prior to adsorption remained sensitive to inhibitors of endosomal acidification, whereas virions treated with low pH after adsorption were resistant. Activation of virions by low pH was closely mimicked by proteinase digestion, suggesting that the two treatments operate through a related mechanism. Although proteinase cleavage of the virion surface proteins D8 and A27 correlated with activation, mutant viruses constructed by individually deleting these genes did not exhibit an activated phenotype. We propose a two-step model of vaccinia virus entry through endosomes, in which activating or unmasking the fusion complex by low pH or by proteinase is rate limiting but does not eliminate a second low-pH step mediating membrane fusion.

* Corresponding author. Mailing address: Laboratory of Viral Diseases, NIAID, NIH, 33 North Drive, MSC 3210, Bethesda, MD 20892. E-mail: BMOSS{at}niaid.nih.gov

{triangledown} Published ahead of print on 6 June 2007.

Journal of Virology, August 2007, p. 8613-8620, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.00606-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Roberts, K. L., Breiman, A., Carter, G. C., Ewles, H. A., Hollinshead, M., Law, M., Smith, G. L. (2009). Acidic residues in the membrane-proximal stalk region of vaccinia virus protein B5 are required for glycosaminoglycan-mediated disruption of the extracellular enveloped virus outer membrane. J. Gen. Virol. 90: 1582-1591 [Abstract] [Full Text]  
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