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Journal of Virology, February 2006, p. 1191-1203, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1191-1203.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Infection-Dependent Nuclear Localization of US17, a Member of the US12 Family of Human Cytomegalovirus-Encoded Seven-Transmembrane Proteins

Subhendu Das, Yelenna Skomorovska-Prokvolit, Fu-Zhang Wang, and Philip E. Pellett*

Department of Molecular Genetics, Section of Virology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue NN10, Cleveland, Ohio 44195

Received 27 September 2005/ Accepted 7 November 2005

The human cytomegalovirus (HCMV) US12 gene family is a group of predicted seven-transmembrane, G-protein-coupled receptor-related proteins, about which little is known. Specific rabbit polyclonal antibodies detected US17 and US18 beginning 54 and 36 h after infection, respectively, with expression of both proteins dependent on viral DNA synthesis. While US14 and US18 are expressed exclusively in the cytoplasm, we unexpectedly found abundant expression of US17 in both the cytoplasm and nucleoplasm. N- and C-terminally tagged versions of US17 were readily detected in the cytoplasm of transfected mammalian cells, but not in nuclei, suggesting that nuclear localization involves other viral proteins or an infection-triggered cellular process. There was no specific colocalization between US17 and other nuclear expressed HCMV-encoded proteins (IE-2, DNA polymerase processivity factor, and pp28/UL99). To determine whether the observed nuclear localization might be the product of a process by which a soluble C-terminal segment of the full-length protein is expressed, we constructed a recombinant virus that incorporates a synthetic epitope at its N terminus, which in conjunction with the antipeptide antibody that targets its predicted cytoplasmic C-terminal segment, enables simultaneous independent detection of both termini. In cells infected with the recombinant, the US17 N and C termini had limited colocalization, with the N-terminal segment not detected in nuclei, supporting the segmentation hypothesis. Consistent with this, a fragment with an apparent molecular size of 10 kDa was detected by immunoblotting. We have identified the first viral example of a seven-transmembrane protein that is either segmented or expressed in nuclei. Further study will be required to learn the mechanism by which this occurs and the function of the nuclear localizing segment. This likely represents yet another mechanism by which a virus has hijacked or modified cellular regulatory pathways for its benefit.

* Corresponding author. Mailing address: Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue NN10, Cleveland, OH 44195. Phone: (216) 445-8411. Fax: (216) 444-2998. E-mail: pelletp{at}ccf.org.

Journal of Virology, February 2006, p. 1191-1203, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1191-1203.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, F.-Z., Weber, F., Croce, C., Liu, C.-G., Liao, X., Pellett, P. E. (2008). Human Cytomegalovirus Infection Alters the Expression of Cellular MicroRNA Species That Affect Its Replication. J. Virol. 82: 9065-9074 [Abstract] [Full Text]  
  • Das, S., Vasanji, A., Pellett, P. E. (2007). Three-Dimensional Structure of the Human Cytomegalovirus Cytoplasmic Virion Assembly Complex Includes a Reoriented Secretory Apparatus. J. Virol. 81: 11861-11869 [Abstract] [Full Text]  


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