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Journal of Virology, May 2002, p. 4441-4455, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4441-4455.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Absence of IE1 p72 Protein Function during Low-Multiplicity Infection by Human Cytomegalovirus Results in a Broad Block to Viral Delayed-Early Gene Expression

Jonathan M. Gawn1 and Richard F. Greaves1,2*

Department of Medicine, Cambridge University Clinical School, Addenbrooke's Hospital, Cambridge CB2 2QQ,1 Virology and Cell Biology Section, Department of Infectious Diseases, Imperial College Faculty of Medicine, St. Mary's Hospital, London W2 1PG, United Kingdom2

Received 24 September 2001/ Accepted 28 January 2002

Human cytomegalovirus (HCMV) ie1 deletion mutant CR208 is profoundly growth deficient after low-multiplicity infection of primary fibroblasts. Previously, we showed that many fewer cells infected with CR208 at low multiplicity accumulated the delayed-early (DE) protein ppUL44 than accumulated the immediate-early 2 (IE2) p86 protein, indicating a high frequency of abortive infections. We now demonstrate that accumulation of all DE proteins tested was defective after low-multiplicity infection in the absence of IE1 p72. Accumulation of the DE proteins pUL57, pUL98, and pUL69 followed a pattern very similar to that of ppUL44 during low-multiplicity CR208 infection. Accumulation of the ppUL112-113 proteins occurred in a greater proportion of cells than other DE proteins during low-multiplicity CR208 infection, but was still deficient relative to wild-type virus. We also show for the first time that steady-state levels of many DE RNAs were reduced during low-multiplicity CR208 infection and that by in situ hybridization of the abundant cytoplasmic 2.7-kb TRL4 DE (ß2.7) RNA, a viral DE RNA followed a defective pattern of accumulation similar to that of ppUL44. Furthermore, transfected DE promoter-reporter constructs were found in transient assays to be considerably less responsive to CR208 infection than to infection by wild-type Towne virus. Our results indicate a general defect in DE gene expression following low-multiplicity HCMV infection in the absence of functional IE1 p72, most probably mediated by reduced transcription of DE genes and by the reduced accumulation of DE RNAs.

* Corresponding author. Mailing address: Virology and Cell Biology Section, Department of Infectious Diseases, Imperial College Faculty of Medicine, St. Mary's Hospital, London W2 1PG, United Kingdom. Phone: 44-20-75943639. Fax: 44-20-77248586. E-mail: richard.greaves{at}ic.ac.uk.

Journal of Virology, May 2002, p. 4441-4455, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4441-4455.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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