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- W1565090329 abstract "Despite being closely related viruses with similar replication cycles, HIV-2replicates more slowly than HIV-1 and produces fewer particles, resulting in alower plasma viral load. Expression of the major structural gene, gag, fromHIV-1 and HIV-2 proviruses was compared to investigate whether this couldplay a role in the difference in particle production observed between HIV-1and HIV-2 infection.Using quantitative RT-PCR, significantly less full-length HIV-2 gag mRNAwas found to be transcribed from its provirus than for HIV-1. Sub-cellularfractionation allowed us to determine HIV-1/2 gag mRNA levels in thenucleus and cytoplasm throughout a time course. RNA export of HIV-2 gagmRNA was shown to be slower than for HIV-1 gag mRNA.HIV-2 full-length gag RNA was shown to be translated much less efficientlythan HIV-1 in a range of cell lines. Both HIV-1 and HIV-2 Gag have beenproposed to be translated by internal ribosome entry. Shutting down capdependenttranslation (by poliovirus-mediated eIF4G cleavage) significantlyreduced translation from both HIV-1/2 gag RNAs, with no evidence ofcompensatory IRES activity. This suggests that cap-dependent translation isthe predominant mechanism for translation of both HIV-1 and HIV-2 RNA.Additional work explored HIV RNA-protein interactions by UV cross-linkingexperiments using cellular proteins. Several proteins differentially binding toHIV-1/2 5’ UTR RNAs were identified and, in particular, a 45 kDa proteinbinding only to the HIV-1 5’ UTR. Attempts were made to characterise theproteins binding with different affinities to HIV-1 and HIV-2 RNAs.Confocal microscopy was used to visualise HIV-1/2 Gag expression withinthe cell. Both HIV-1 and HIV-2 Gag expression was shown to be reducedwhen siRNA was used to inhibit the cellular clathrin adaptor protein AP-1.In conclusion, HIV-2 Gag gene expression was found to be less efficient thanHIV-1 at the level of transcription, RNA export and translation. Future workwill continue to investigate the mechanisms behind these differences." @default.
- W1565090329 created "2016-06-24" @default.
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- W1565090329 date "2012-01-01" @default.
- W1565090329 modified "2023-09-28" @default.
- W1565090329 title "A comparison of HIV-1 and HIV-2 gag gene expression" @default.
- W1565090329 hasPublicationYear "2012" @default.
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