A short stretch of T-rich sequences immediately upstream of the polypurine tract (PPT) is highly conserved in the proviral genomes of human and simian immunodeficiency viruses (HIV and SIV) To investigate whether this """"""""U-box"""""""" influences SIVmac239 replication, we analyzed the properties of mutants with changes in this region of the viral genome All mutants were either retarded in their growth (up to one month delay) or did not replicate detectably in CEMx174 cells When U-box mutants did replicate detectably, compensatory changes were consistently observed in the viral genome The most common compensatory change was the acquisition of thymidines immediately upstream of the PPT, but marked expansion in the length of the PPT was also observed U-box mutants produced transiently by transfection were severely impaired in their ability to produce reverse transcripts in infectivity assays Analysis of transiently produced mutant virus revealed no defect in RNA pack agin g or virus assembly These results identify a new structural element important for an early step in the viral life cycle that includes reverse transcription PUBLICATIONS Ilyinskii, PO and Desrosiers, RC Identification of a sequence element immediately upstream of the polypurine tract that is essential for replication of simian immunodeficiency virus EMBO J 1998; 17:3766-3774

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-41
Application #
6591300
Study Section
Project Start
2002-05-01
Project End
2003-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
41
Fiscal Year
2002
Total Cost
$111,112
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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Ma, Qi; Ruan, Hongyu; Peng, Lisheng et al. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A 114:E8760-E8769
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