title: The HIV-1 leader RNA is exquisitely sensitive to structural changes.
abstract: The untranslated leader of the HIV-1 RNA genome is highly structured and contains multiple replication signals. We probed in detail the sequence requirements of a small single-stranded domain using a combination of in silico, in vitro and in vivo virus experiments. Although 'structure-neutral' mutations can be designed by RNA prediction algorithms, experimental follow-up studies nearly always demonstrate local or regional RNA structure changes. Our results indicate that the wild-type HIV-1 RNA sequence has been selected from total sequence space as a unique solution to present critical replication signals in the context of a complex leader structure with small intervening single-stranded segments.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: n.vanbel@amc.uva.nl.
authors.forename: Nikki
authors.initials: N
authors.lastname: van Bel
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: a_ghabri@live.nl.
authors.forename: Anouar
authors.initials: A
authors.lastname: Ghabri
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: a.t.das@amc.uva.nl.
authors.forename: Atze T
authors.initials: AT
authors.lastname: Das
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: b.berkhout@amc.uva.nl.
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D009690:Nucleic Acid Conformation; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D014779:Virus Replication
chemical_list: D022661:RNA, Untranslated; D012367:RNA, Viral
keywords: HIV-1 RNA; RNA architecture; RNA sequence and structure; Virus evolution