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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-8-12
pubmed:abstractText
In utero fetal infection of rubella virus (RV), a positive-stranded RNA virus, frequently induces birth defects if contracted in the first trimester of pregnancy. The underlying mechanism of RV-induced birth defects is not known. Birth defects are also common in certain DNA viral infections such as human cytomegalovirus (HCMV). During HCMV infection, one of its proteins interacts with a cell growth regulatory protein, the retinoblastoma protein (Rb) and stimulates DNA synthesis which is associated with chromosomal damage and cellular mitotic arrest. These affects have been implicated in HCMV induced teratogenesis. Since RV and HCMV both cause teratogenesis, we postulated that during RV infection, a virus-encoded protein might interact with Rb and affect fetal cell growth. In the present study, we have identified a known Rb-binding motif, L x C x E (LPCAE) in the carboxy-terminal half of the putative replicase (NSP90) of RV and demonstrated that the C-terminal region specifically binds to GST-Rb in vitro. Further, by coimmunoprecipitating NSP90 and Rb using specific antibodies to respective proteins, we have confirmed that NSP90 specifically binds to Rb in vivo as well. In addition, RV replication was shown to be less in null-mutant (Rb-/-) mouse embryonic fibroblast cells than in wild-type (Rb+/+) cells, suggesting a possible physiological role for this interaction. Thus, in facilitating RV replication, binding of NSP90 to Rb potentially alters the cell growth regulatory property of Rb, and this could be one of the initial steps in RV-induced teratogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0920-8569
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
177-83
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
The rubella virus putative replicase interacts with the retinoblastoma tumor suppressor protein.
pubmed:affiliation
Division of Viral Products, University of Leipzig, Germany. Atreya@A1.CBER.FDA.GOV
pubmed:publicationType
Journal Article