Cytomegalovirus
Return to Library
|
Free Cytomegalovirus Articles |
|
|
|
|
Studies from University of Heidelberg yield new information about cytomegalovirus
2009 OCT 19 - (NewsRx.com) -- According to a study from Heidelberg, Germany, "Phosphoprotein ppUL44 of the human cytomegalovirus (HCMV) DNA polymerase plays an essential role in viral replication, conferring processivity to the DNA polymerase catalytic subunit pUL54 by tethering it to the DNA. Here, for the first time, we examine in living cells the function of the highly flexible loop of ppUL44 (UL44-FL; residues 162 to 174 [PHTRVKRNVKKAP(174)]), which has been proposed to be directly involved in ppUL44's interaction with DNA." "In particular, we use a variety of approaches in transfected cells to characterize in detail the behavior of ppUL44 Delta loop, a mutant derivative in which three of the five basic residues within UL44-FL are replaced by nonbasic amino acids. Our results indicate that ppUL44 Delta loop is functional in dimerization and binding to pUL54 but strongly impaired in binding nuclear structures within the nucleus, as shown by its inability to form nuclear speckles, reduced nuclear accumulation, and increased intranuclear mobility compared to wild-type ppUL44. Moreover, analysis of cellular fractions after detergent and DNase treatment indicates that ppUL44 Delta loop is strongly reduced in DNA-binding ability, in similar fashion to ppUL44-L86A/L87A, a point mutant derivative impaired in dimerization. Finally, ppUL44 Delta loop fails to transcomplement HCMV oriLyt-dependent DNA replication in cells and also inhibits replication in the presence of wild-type ppUL44, possibly via formation of heterodimers defective for double-stranded DNA binding," wrote G. Alvisi and colleagues, University of Heidelberg. The researchers concluded: "UL44-FL thus emerges for the first time as an important determinant for HCMV replication in cells, with potential implications for the development of novel antiviral approaches by targeting HCMV replication." Alvisi and colleagues published the results of their research in the Journal of Virology (The Flexible Loop of the Human Cytomegalovirus DNA Polymerase Processivity Factor ppUL44 Is Required for Efficient DNA Binding and Replication in Cells. Journal of Virology, 2009;83(18):9567-9576). For additional information, contact G. Alvisi, University of Heidelberg, Dept. of Molecular Virology, Neuenheimer Feld 345, D-69120 Heidelberg, Germany. The publisher of the Journal of Virology can be contacted at: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA. Keywords: Germany, Heidelberg, Amino Acids, Behavior, Cytomegalovirus, DNA, Drugs, Enzyme Research, Pharmaceuticals, Polymerase, Therapy, Treatment, Viral, Virology, Virus, University of Heidelberg. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
|
