title: The hematopoietic cell-specific Rho GTPase inhibitor ARHGDIB/D4GDI limits HIV type 1 replication.
abstract: Rho GTPases are able to influence the replication of human immunodeficiency virus type 1 (HIV-1). However, little is known about the regulation of HIV-1 replication by guanine nucleotide dissociation inhibitors (GDIs), one of the three major regulators of the Rho GTPase activation cycle. From a T cell-based cDNA library screening, ARHGDIB/RhoGDIβ, a hematopoietic lineage-specific GDI family protein, was identified as a negative regulator of HIV-1 replication. Up-regulation of ARHGDIB attenuated the replication of HIV-1 in multiple T cell lines. The results showed that (1) a significant portion of RhoA and Rac1, but not Cdc42, exists in the GTP-bound active form under steady-state conditions, (2) ectopic ARHGDIB expression reduced the F-actin content and the active forms of both RhoA and Rac1, and (3) HIV-1 infection was attenuated by either ectopic expression of ARHGDIB or inhibition of the RhoA signal cascade at the HIV-1 Env-dependent early phase of the viral life cycle. This is in good agreement with the previous finding that RhoA and Rac1 promote HIV-1 entry by increasing the efficiency of receptor clustering and virus-cell membrane fusion. In conclusion, the ARHGDIB is a lymphoid-specific intrinsic negative regulator of HIV-1 replication that acts by simultaneously inhibiting RhoA and Rac1 functions.
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Emiko
authors.initials: E
authors.lastname: Urano
authors.forename: Kosuke
authors.initials: K
authors.lastname: Miyauchi
authors.forename: Reiko
authors.initials: R
authors.lastname: Ichikawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Hamatake
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ebina
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.forename: Jun
authors.initials: J
authors.lastname: Komano
mesh_terms: D015153:Blotting, Western; D004261:DNA Replication; D005434:Flow Cytometry; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction; D015854:Up-Regulation; D014779:Virus Replication / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: C569658:ARHGDIB protein, human; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins