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Journal of Virology, June 2002, p. 5748-5758, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5748-5758.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus US7, US8, US9, and US10 Are Cytoplasmic Glycoproteins, Not Found at Cell Surfaces, and US9 Does Not Mediate Cell-to-Cell Spread

Mary T. Huber,^, Roman Tomazin, Todd Wisner, Jessica Boname,^, and David C. Johnson^*

Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon 97201

Received 26 November 2001/ Accepted 15 February 2002

Human cytomegalovirus (HCMV) expresses a large number of membrane proteins with unknown functions. One class of these membrane proteins apparently acts to allow HCMV to escape detection by the immune system. The best characterized of these are the glycoproteins encoded within the US2 to US11 region of the HCMV genome that mediate resistance to CD8⁺ and CD4⁺ T cells. US2, US3, US6, and US11 block various aspects of the major histocompatibility complex (MHC) class I and class II antigen presentation pathways, functioning in cytoplasmic membranes to cause retention, degradation, or mislocalization of MHC proteins. Distantly homologous genes in this region, US7, US8, US9, and US10, are not well characterized. Here, we report expression of the glycoproteins encoded by US7 to US10 by using replication-defective adenovirus (Ad) vectors. US7, US9, and US10 remained sensitive to endoglycosidase H and were exclusively or largely present in the endoplasmic reticulum (ER) as determined by confocal microscopy. US8 reached the Golgi apparatus and trans-Golgi network and was more quickly degraded. Previous studies suggested that US9 could localize to cell junctions and mediate cell-to-cell spread in ARPE-19 retinal epithelial cells. We found no evidence of US9 at cell junctions of HEC-1A epithelial cells. HCMV recombinants lacking US9 produced smaller plaques on ARPE-19 cell monolayers but also exhibited defects in virus replication compared with wild-type HCMV in these cells. Other HCMV recombinants constructed in a similar fashion that were able to express US9 also produced small plaques and some of these exhibited defects in production of infectious progeny in ARPE-19 cells. Thus, there was no correlation between defects in cell-to-cell spread (plaque size) and loss of expression of US9, and it is possible that US9^- mutants produce smaller plaques because they produce fewer progeny. Together, our results do not support the hypothesis that US9 plays a direct role in HCMV cell-to-cell spread.

Present address: Xenon Genetics, Vancouver, BC V6T1Z3, Canada.

Present address: Dept. of Pathology, Cambridge University, Cambridge, United Kingdom.

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