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Journal of Virology, April 2005, p. 4066-4079, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4066-4079.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antigenic Domain 1 Is Required for Oligomerization of Human Cytomegalovirus Glycoprotein B

Departments of Pediatrics,¹ Microbiology,² Neurobiology, University of Alabama School of Medicine, Birmingham, Alabama,³ Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Portland, Oregon,⁴ Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen, Germany⁵

Received 8 September 2004/ Accepted 4 November 2004

Human cytomegalovirus (HCMV) glycoprotein B (gB) is an abundant virion envelope protein that has been shown to be essential for the infectivity of HCMV. HCMV gB is also one of the most immunogenic virus-encoded proteins, and a significant fraction of virus neutralizing antibodies are directed at gB. A linear domain of gB designated AD-1 (antigenic domain 1) represents a dominant antibody binding site on this protein. AD-1 from clinical isolates of HCMV exhibits little sequence variation, suggesting that AD-1 plays an essential role in gB structure or function. We investigated this possibility by examining the role of AD-1 in early steps of gB synthesis. Our results from studies using eukaryotic cells indicated that amino acid (aa) 635 of the gB sequence represented the carboxyl-terminal limit of this domain and that deletion of aa 560 to 640 of the gB sequence resulted in loss of AD-1 expression. AD-1 was shown to be required for oligomerization of gB. Mutation of cysteine at either position 573 or 610 in AD-1 resulted in loss of its reactivity with AD-1-specific monoclonal antibodies and gB oligomerization. Infectious virus could not be recovered from HCMV bacterial artificial chromosomes following introduction of these mutations into the HCMV genome, suggesting that AD-1 was an essential structural domain required for gB function in the replicative cycle of HCMV. Sequence alignment of AD-1 with homologous regions of gBs from other herpesviruses demonstrated significant relatedness, raising the possibility that this domain may contribute to multimerization of gBs in other herpesviruses.

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