Human Immunodeficiency Virus Type 1 (HIV-1) is a retrovirus that infects humans. The HIV-1 genomic RNA (gRNA) has two fates; it serves as the genome that is packaged into viral particles and as an mRNA template for translation of viral proteins. No currently approved antivirals target viral packaging and assembly; understanding the mechanism of gRNA translation and packaging is critical for developing therapeutics targeting the late stages of the HIV-1 lifecycle. Previous work has established that viral RNA transcriptional start sites are heterogeneous and that the 5`UTR folds differently depending on 5` guanosine content (1G, 2G, or 3G). The 3G gRNA is the predominant viral RNA transcription product, yet the minor 1G transcript is selectively packaged into assembling virions. Previous work also showed when structural differences between 1G and 3G transcripts are abrogated, the 1G packaging preference is also eliminated. Using an in vitro luciferase reporter translation assay, we have shown that mRNAs encoding the 3G 5’UTR were translated significantly more efficiently than those encoding 1G 5’UTRs. Whether structural differences result in preferential 3G translation is unclear. We hypothesize that differences in translation are attributed to conformational differences rather than simply the number of 5’ guanosines. We prepared 1G/3G RNA constructs containing zero, one or two terminal 5’ hairpins of the gRNA but lacking downstream 5’UTR sequences; these RNAs are expected to have similar 1G/3G structures. In vitro translation assays support the conclusion that structural differences in the 5’UTR are responsible for differences in translational efficiency. 

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Eckerd College, Madeline Sheppard: mcsheppard@eckerd.edu

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