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The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA

Keating, Cameron P., Hill, Melissa K., Hawkes, David J., Smyth, Redmond P., Isel, Catherine, Le, Shu-Yun, Palmenberg, Ann C., Marshall, John A., Marquet, Roland, Nabel, Gary J. and Mak, Johnson 2009, The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA, Nucleic acids research, vol. 37, no. 3, pp. 945-956, doi: 10.1093/nar/gkn1015.

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Title The A-rich RNA sequences of HIV-1 pol are important for the synthesis of viral cDNA
Author(s) Keating, Cameron P.
Hill, Melissa K.
Hawkes, David J.
Smyth, Redmond P.
Isel, Catherine
Le, Shu-Yun
Palmenberg, Ann C.
Marshall, John A.
Marquet, Roland
Nabel, Gary J.
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Journal name Nucleic acids research
Volume number 37
Issue number 3
Start page 945
End page 956
Total pages 12
Publisher Oxford University Press
Place of publication Oxford, England
Publication date 2009
ISSN 0305-1048
1362-4962
Keyword(s) adenine
base sequence
cell line
codon
dimerization
complementary DNA
viral DNA
pol genes
HIV-1
nucleic acid conformation
regulatory sequences
ribonucleic acid
reverse transcription
viral RNA
viral proteins
virion
virus internalization
virus replication
Summary The bias of A-rich codons in HIV-1 pol is thought to be a record of hypermutations in viral genomes that lack biological functions. Bioinformatic analysis predicted that A-rich sequences are generally associated with minimal local RNA structures. Using codon modifications to reduce the amount of A-rich sequences within HIV-1 genomes, we have reduced the flexibility of RNA sequences in pol to analyze the functional significance of these A-rich ‘structurally poor’ RNA elements in HIV-1 pol. Our data showed that codon modification of HIV-1 sequences led to a suppression of virus infectivity by 5–100-fold, and this defect does not correlate with, viral entry, viral protein expression levels, viral protein profiles or virion packaging of genomic RNA. Codon modification of HIV-1 pol correlated with an enhanced dimer stability of the viral RNA genome, which was associated with a reduction of viral cDNA synthesis both during HIV-1 infection and in a cell free reverse transcription assay. Our data provided direct evidence that the HIV-1 A-rich pol sequence is not merely an evolutionary artifact of enzyme-induced hypermutations, and that HIV-1 has adapted to rely on A-rich RNA sequences to support the synthesis of viral cDNA during reverse transcription, highlighting the utility of using ‘structurally poor’ RNA domains in regulating biological process.
Language eng
DOI 10.1093/nar/gkn1015
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 ©2009, Oxford University Press
Free to Read? Yes
Use Rights Creative Commons Attribution non-commercial licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047564

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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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.