title: The relationship between HIV-1 genome RNA dimerization, virion maturation and infectivity.
abstract: The relationship between virion protein maturation and genomic RNA dimerization of human immunodeficiency virus type 1 (HIV-1) remains incompletely understood. We have constructed HIV-1 Gag cleavage site mutants to enable the steady state observation of virion maturation steps, and precisely study Gag processing, RNA dimerization, virion morphology and infectivity. Within the virion maturation process, the RNA dimer stabilization begins during the primary cleavage (p2-NC) of Pr55 Gag. However, the primary cleavage alone is not sufficient, and the ensuing cleavages are required for the completion of dimerization. From our observations, the increase of cleavage products may not put a threshold on the transition from fragile to stable dimeric RNA. Most of the RNA dimerization process did not require viral core formation, and particle morphology dynamics during viral maturation did not completely synchronize with the transition of dimeric RNA status. Although the endogenous virion RT activity was fully acquired at the initial step of maturation, the following process was necessary for viral DNA production in infected cell, suggesting the maturation of viral RNA/protein plays critical role for viral infectivity other than RT process.
authors.affiliation: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University Suita, Osaka 565-0871, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ohishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Sayuri
authors.initials: S
authors.lastname: Sakuragi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shioda
authors.forename: Kouichi
authors.initials: K
authors.lastname: Sano
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sakuragi
mesh_terms: D002460:Cell Line; D019281:Dimerization; D016679:Genome, Viral; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D009154:Mutation; D011498:Protein Precursors / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014771:Virion / Q000648:ultrastructure; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C071884:NCP7 protein, Human immunodeficiency virus 1; D011498:Protein Precursors; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase