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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,dagger 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 complex branched concatemers, and unstable spherical precursor capsids termed procapsids are thought to be the substrates for the DNA-packaging reaction. In addition, seven viral proteins are required for packaging, although their individual functions are undefined. By analogy to well-characterized bacteriophage systems, the association of these 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 are known to associate with different forms of stable capsids, their association with procapsids has not been tested. Therefore, we isolated HSV-1 procapsids from infected cells and used Western blotting to identify the packaging proteins present. Procapsids contained UL15 and UL28 proteins; the levels of both proteins are 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 reduced in procapsids relative to that in more mature B-capsids. Moreover, C-capsids contained the highest level of UL25 protein, 15-fold higher than that in procapsids. Our results support current hypotheses on HSV DNA packaging: (i) transient association of UL15 and UL28 proteins with maturing capsids is consistent with their proposed involvement in site-specific cleavage of the viral DNA (terminase activity); (ii) the UL6 protein may be an integral component of the capsid shell; and (iii) the UL25 protein may associate with capsids after scaffold loss and DNA packaging, sealing the DNA within capsids.

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

dagger Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

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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