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Journal of Virology, October 2008, p. 10247-10261, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01035-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Vaccinia Virus Gene I2L Encodes a Membrane Protein with an Essential Role in Virion Entry

R. Jeremy Nichols,^, Eleni Stanitsa,^, Bethany Unger, and Paula Traktman^*

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Received 16 May 2008/ Accepted 6 August 2008

The previously unstudied vaccinia virus gene I2L is conserved in all orthopoxviruses. We show here that the 8-kDa I2 protein is expressed at late times of infection, is tightly associated with membranes, and is encapsidated in mature virions. We have generated a recombinant virus in which I2 expression is dependent upon the inclusion of tetracycline in the culture medium. In the absence of I2, the biochemical events of the viral life cycle progress normally, and virion morphogenesis culminates in the production of mature virions. However, these virions show an 400-fold reduction in specific infectivity due to an inability to enter target cells. Several proteins that have been previously identified as components of an essential entry/fusion complex are present at reduced levels in I2-deficient virions, although other membrane proteins, core proteins, and DNA are encapsidated at normal levels. A preliminary structure/function analysis of I2 has been performed using a transient complementation assay: the C-terminal hydrophobic domain is essential for protein stability, and several regions within the N-terminal hydrophilic domain are essential for biological competency. I2 is thus yet another component of the poxvirus virion that is essential for the complex process of entry into target cells.

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* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. Phone: (414) 456-8253. Fax: (414) 456-6535. E-mail: ptrakt{at}mcw.edu

Published ahead of print on 13 August 2008.

Present address: MRC Protein Phosphorylation Unit, University of Dundee, Dundee, United Kingdom.

R.J.N. and E.S. contributed equally to this work.

Present address: McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706.

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Journal of Virology, October 2008, p. 10247-10261, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01035-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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