Herpes Simplex Virus DNA Cleavage and Packaging Proteins Associate with the Procapsid prior to Its Maturation

doi:10.1128/JVI.75.2.687-698.2001

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Journal of Virology, January 2001, p. 687-698, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.687-698.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Herpes Simplex Virus DNA Cleavage and Packaging Proteins Associate with the Procapsid prior to Its Maturation

Amy K. Sheaffer,¹ William W. Newcomb,² Min Gao,¹ Dong Yu,³^, Sandra K. Weller,³ Jay C. Brown,² and Daniel J. Tenney¹^,^*

Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492¹; Department of Microbiology, University of Virginia Health System, Charlottesville, Virginia 22908²; and Department of Microbiology, University of Connecticut Health Center, Farmington, Connecticut 06030³

Received 4 August 2000/Accepted 17 October 2000

Packaging of DNA into preformed capsids is a fundamental early event in the assembly of herpes simplex virus type 1 (HSV-1)virions. Replicated viral DNA genomes, in the form of complexbranched concatemers, and unstable spherical precursor capsidstermed procapsids are thought to be the substrates for the DNA-packagingreaction. In addition, seven viral proteins are required for packaging,although their individual functions are undefined. By analogyto well-characterized bacteriophage systems, the association ofthese proteins with various forms of capsids, including procapsids,might be expected to clarify their roles in the packaging process.While the HSV-1 UL6, UL15, UL25, and UL28 packaging proteins areknown to associate with different forms of stable capsids, theirassociation with procapsids has not been tested. Therefore, weisolated HSV-1 procapsids from infected cells and used Westernblotting to identify the packaging proteins present. Procapsidscontained UL15 and UL28 proteins; the levels of both proteinsare diminished in more mature DNA-containing C-capsids. In contrast,UL6 protein levels were approximately the same in procapsids,B-capsids, and C-capsids. The amount of UL25 protein was reducedin procapsids relative to that in more mature B-capsids. Moreover,C-capsids contained the highest level of UL25 protein, 15-foldhigher than that in procapsids. Our results support current hypotheseson HSV DNA packaging: (i) transient association of UL15 and UL28proteins with maturing capsids is consistent with their proposedinvolvement in site-specific cleavage of the viral DNA (terminaseactivity); (ii) the UL6 protein may be an integral component ofthe capsid shell; and (iii) the UL25 protein may associate withcapsids after scaffold loss and DNA packaging, sealing the DNAwithincapsids.

^* Corresponding author. Mailing address: Department of Virology, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 ResearchParkway, Wallingford, CT 06492. Phone: (203) 677-7846. Fax: (203)677-6088. E-mail: Daniel.Tenney{at}bms.com.

Present address: Department of Molecular Biology, Princeton University, Princeton, NJ08544.

Journal of Virology, January 2001, p. 687-698, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.687-698.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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