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Journal of Virology, August 2003, p. 8541-8547, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8541-8547.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Microtubule Network Facilitates Nuclear Targeting of Human Cytomegalovirus Capsid

K. Ogawa-Goto,1,2* K. Tanaka,1 W. Gibson,3 E. Moriishi,1 Y. Miura,1,2 T. Kurata,1 S. Irie,2 and T. Sata1*

Department of Pathology, National Institute of Infectious Diseases, Shinjuku, Tokyo 162-8640,1 Nippi Research Institute of Biomatrix, Adachi, Tokyo 120-8601, Japan,2 Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 212053

Received 23 December 2002/ Accepted 12 May 2003

We assessed the requirement of the host cytoskeleton for the intracytosolic transport of incoming human cytomegalovirus (HCMV) capsids. Treatments with microtubule (MT)-depolymerizing drugs nocodazole and colchicine led to a drastic decrease in levels of IE1 antigen, whereas cytochalasin B had no effect on the level of IE1 as determined by Western blot analyses. Sequential treatment including nocodazole washout and removal of cell surface virion revealed that HCMV entry into the cells occurred normally in the absence of the MT network. This finding was also supported by data obtained by monitoring pUL83 signals with an immunofluorescent assay (IFA). Furthermore, we demonstrated a close association of incoming HCMV capsids with MTs by IFA and ultrastructural analyses. In the absence of the MT network, the capsids which had entered the cytoplasm did not move to close proximity of the nucleus. These data suggest that HCMV capsids associate with the MT network to facilitate their own movement to the nucleus before the onset of immediate-early (IE) gene expression and that this association is required to start efficient IE gene expression.

* Corresponding author. Mailing address: Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111, ext. 2626. Fax: 81-3-5285-1189. E-mail for K. Ogawa-Goto: kgoto{at}nih.go.jp. E-mail for T. Sata: tsata{at}nih.go.jp.

Journal of Virology, August 2003, p. 8541-8547, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8541-8547.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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