Analysis of the contribution of reverse transcriptase and integrase proteins to retroviral RNA dimer conformation

被引:17
作者
Buxton, P
Tachedjian, G
Mak, J
机构
[1] Macfarlane Burnet Inst Med Res & Publ Hlth, Virol Program, Melbourne, Vic 3004, Australia
[2] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia
[3] Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia
[4] Monash Univ, Dept Med, Prahran, Vic, Australia
关键词
D O I
10.1128/JVI.79.10.6338-6348.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
All retroviruses contain two copies of genomic RNA that are linked noncovalently. The dimeric RNA of human immunodeficiency virus type I (HIV-1) undergoes rearrangement during virion maturation, whereby the dimeric RNA genome assumes a more stable conformation. Previously, we have shown that the packaging of the HIV-1 polymerase (Pol) proteins reverse transcriptase (RT) and integrase (IN) is essential for the generation of the mature RNA dimer conformation. Analysis of HIV-1 mutants that are defective in processing of Poll showed that these mutant virions contained altered dimeric RNA conformation, indicating that the mature RNA dimer conformation in HIV-1 requires the correct proteolytic processing of Pol. The HIV-1 Poll proteins are multimeric in their mature enzymatically active forms; RT forms a heterodimer, and IN appears to form a homotetramer. Using RT and IN multimerization defective mutants, we have found that dimeric RNA from these mutant virions has the same stability and conformation as wild-type RNA dimers, showing that the mature enzymatically active RT and IN proteins are dispensable for the generation of mature RNA dimer conformation. This also indicated that formation of the mature RNA dimer structure occurs prior to RT or IN maturation. We have also investigated the requirement of Pol for RNA dimerization in both Mason-Pfizer monkey virus (M-PMV) and Moloney murine leukemia virus (MoMuLV) and found that in contrast to HIV-1, Pol is dispensable for RNA dimer maturation in M-PMV and MoMuLV, demonstrating that the requirement of Pol in retroviral RNA dimer maturation is not conserved among all retroviruses.
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页码:6338 / 6348
页数:11
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