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Proline residues within spacer peptide p1 are important for human immunodeficiency virus type 1 infectivity, protein processing, and genomic RNA dimer stability

Hill, Melissa K., Shehu-Xhilaga, Miranda, Crowe, Suzanne M. and Mak, Johnson 2002, Proline residues within spacer peptide p1 are important for human immunodeficiency virus type 1 infectivity, protein processing, and genomic RNA dimer stability, Journal of virology, vol. 76, no. 22, pp. 11245-11253, doi: 10.1128/JVI.76.22.11245-11253.2002.

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Title Proline residues within spacer peptide p1 are important for human immunodeficiency virus type 1 infectivity, protein processing, and genomic RNA dimer stability
Author(s) Hill, Melissa K.
Shehu-Xhilaga, Miranda
Crowe, Suzanne M.
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Journal name Journal of virology
Volume number 76
Issue number 22
Start page 11245
End page 11253
Total pages 9
Publisher American Society for Microbiology
Place of publication Washington, D. C.
Publication date 2002-11
ISSN 0022-538X
1098-5514
Keyword(s) gag protein
genomic RNA
messenger RNA
pol protein
polyprotein
proline
Summary The full-length human immunodeficiency virus type 1 (HIV-1) mRNA encodes two precursor polyproteins, Gag and GagProPol. An infrequent ribosomal frameshifting event allows these proteins to be synthesized from the same mRNA in a predetermined ratio of 20 Gag proteins for each GagProPol. The RNA frameshift signal consists of a slippery sequence and a hairpin stem-loop whose thermodynamic stability has been shown in in vitro translation systems to be critical to frameshifting efficiency. In this study we examined the frameshift region of HIV-1, investigating the effects of altering stem-loop stability in the context of the complete viral genome and assessing the role of the Gag spacer peptide p1 and the GagProPol transframe (TF) protein that are encoded in this region. By creating a series of frameshift region mutants that systematically altered the stability of the frameshift stem-loop and the protein sequences of the p1 spacer peptide and TF protein, we have demonstrated the importance of stem-loop thermodynamic stability in frameshifting efficiency and viral infectivity. Multiple changes to the amino acid sequence of p1 resulted in altered protein processing, reduced genomic RNA dimer stability, and abolished viral infectivity. The role of the two highly conserved proline residues in p1 (position 7 and 13) was also investigated. Replacement of the two proline residues by leucines resulted in mutants with altered protein processing and reduced genomic RNA dimer stability that were also noninfectious. The unique ability of proline to confer conformational constraints on a peptide suggests that the correct folding of p1 may be important for viral function.
Language eng
DOI 10.1128/JVI.76.22.11245-11253.2002
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2002, American Society for Microbiology
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047535

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.