title: Substitution of the myristoylation signal of human immunodeficiency virus type 1 Pr55Gag with the phospholipase C-delta1 pleckstrin homology domain results in infectious pseudovirion production.
abstract: The matrix domain (MA) of human immunodeficiency virus type 1 Pr55Gag is covalently modified with a myristoyl group that mediates efficient viral production. However, the role of myristoylation, particularly in the viral entry process, remains uninvestigated. This study replaced the myristoylation signal of MA with a well-studied phosphatidylinositol 4,5-biphosphate-binding plasma membrane (PM) targeting motif, the phospholipase C-delta1 pleckstrin homology (PH) domain. PH-Gag-Pol PM targeting and viral production efficiencies were improved compared with Gag-Pol, consistent with the estimated increases in Gag-PM affinity. Both virions were recovered in similar sucrose density-gradient fractions and had similar mature virion morphologies. Importantly, PH-Gag-Pol and Gag-Pol pseudovirions had almost identical infectivity, suggesting a dispensable role for myristoylation in the virus life cycle. PH-Gag-Pol might be useful in separating the myristoylation-dependent processes from the myristoylation-independent processes. This the first report demonstrating infectious pseudovirion production without myristoylated Pr55Gag.
authors.affiliation: Kitasato Institute of Life Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan.|AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Urano
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Aoki
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Futahashi
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Kitasato Institute of Life Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Komano
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015685:Fusion Proteins, gag-pol / Q000378:metabolism; D015683:Gene Products, gag; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D019814:Myristic Acid / Q000378:metabolism*; D054803:Phospholipase C delta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D001798:Blood Proteins; D015685:Fusion Proteins, gag-pol; D015683:Gene Products, gag; D010750:Phosphoproteins; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; C039077:platelet protein P47; D019814:Myristic Acid; D054803:Phospholipase C delta