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

AUTOR(ES)

Gawn, Jonathan M.

FONTE

American Society for Microbiology

RESUMO

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 (β2.7) 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.

Documentos Relacionados

• Defective Growth Correlates with Reduced Accumulation of a Viral DNA Replication Protein after Low-Multiplicity Infection by a Human Cytomegalovirus ie1 Mutant
• Regulation of delayed-early gene transcription by dual TATA boxes.
• Interspersed Homologous DNA of Autographa californica Nuclear Polyhedrosis Virus Enhances Delayed-Early Gene Expression
• SUMOylation of the Human Cytomegalovirus 72-Kilodalton IE1 Protein Facilitates Expression of the 86-Kilodalton IE2 Protein and Promotes Viral Replication
• Functional mapping of a trans-activating gene required for expression of a baculovirus delayed-early gene.