RNA, but not necessarily the viral genome, is required for HIV-1 assembly, and roughly a third of the RNA in retroviral particles is host-encoded. The exquisite selectivity observed in some host RNAs'incorporation suggests specific molecular interactions are involved in their recruitment. However, the determinants and mechanisms governing incorporation of these host components into virions, and whether or not these RNAs affect virus properties, have remained largely unexplored. The proposed work examines the determinants of specific host RNAs'virion incorporation for both HIV-1 and the gammaretrovirus, MLV. This revised application includes preliminary data that solidify evidence for the active recruitment of some RNAs into retroviral particles and exclusion of other. The broad long term objectives are to advance general understanding of intracellular viral processes such as assembly, to determine which properties and molecular interactions dictate host small RNA packaging, and to address whether or not these small host RNAs affect retrovirus biology. Defining the molecular interactions necessary for the incorporation of these RNAs may increase the repertoire of potential antiretroviral targets.
The specific aims are (1) to define the cis-acting determinants of 7SL RNA packaging and to explore whether host RNA-virus interactions appear direct or if they correlate with host protein recruitment (2) to exchange transcription signals to test the hypothesis that transcription by pol III predisposes an RNA for encapsidation and (3) to establish conditions that provide a selective advantage for 7SL RNA exclusion.
These studies will enhance understanding of highly conserved yet poorly understood components of viruses like HIV-1. Understanding how human RNA molecules are recruited into viruses may help clarify how progeny viruses form during infections, and may reveal new vulnerabilities that can be targeted in the development of new classes of antiviral drugs.
|Keene, Sarra E; Telesnitsky, Alice (2012) cis-Acting determinants of 7SL RNA packaging by HIV-1. J Virol 86:7934-42|
|Keene, Sarra E; King, Steven R; Telesnitsky, Alice (2010) 7SL RNA is retained in HIV-1 minimal virus-like particles as an S-domain fragment. J Virol 84:9070-7|
|Telesnitsky, Alice (2010) Retroviruses: Molecular Biology, Genomics and Pathogenesis. Future Virol 5:539-543|
|Garcia, Eric L; Onafuwa-Nuga, Adewunmi; Sim, Soyeong et al. (2009) Packaging of host mY RNAs by murine leukemia virus may occur early in Y RNA biogenesis. J Virol 83:12526-34|