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Abstract
HIV encapsidates viral genomic RNA and APOBEC3G in mRNA processing bodies
R. Aguiar1, X. Contreras2, A. Tanuri1, M. Peterlin2
Background: Retroviral assembly is a complex process between viral proteins and RNA as well as host cell factors and machineries. In particular, two copies of the full length genomic RNA must be incorporated into new viral particles. However, these transcripts also exist in a pool of mRNA that is translated for the expression of viral structural proteins, such as Gag and GagPol. Thus, the virus has to select and package the full length genomic RNA over the vast excess of cellular and subgenomic viral mRNA species. This process must be specific and regulated. Indeed, we found that the encapsidation of HIV RNA requires mRNA processing (P) bodies. P bodies are cytoplasmic foci that aggregate translationally repressed mRNA species, for which they serve as transient storage compartments.
Methods: P bodies were depleted with siRNAs against GW182 or RCK in TZM-Bl cells. These cells were infected 60 h later with HIV, washed extensively and after two days, new viral particles were harvested from these cells. Infectivity of progeny virions was determined on fresh TZM-Bl cells by quantifying the luciferase activity.
Results: HIV produced from P body-depleted cells was up to 10-fold less infectious than that from control cells. Although the disruption of these foci had no effect on the production of virus like particles, they contained no genomic RNA and were not infectious. Moreover, genomic RNA and Gag proteins co-localized and co-precipitated with components of P bodies, which were subsequently incorporated into viral particles. Finally, these foci were also required for the incorporation of the host restriction factor APOBEC3G into progeny virions.
Conclusions: Our results demonstrate that specific cellular RNA processing machineries are subverted by retroviruses, such as HIV, for their proper assembly into infectious viral particles. This observation suggests that interfering with P bodies could represent a general future anti-retroviral strategy.
5th IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
TUAA103
Suggested Citation
"R.Aguiar, et al.
HIV encapsidates viral genomic RNA and APOBEC3G in mRNA processing bodies .
:
5th IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
TUAA103 "
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