Inhibiting the Arp2/3 complex limits infection of both intracellular mature vaccinia virus and primate lentiviruses.
Characterizing cellular factors involved in the life cycle of human immunodeficiency virus type 1 (HIV-1) is an initial step toward controlling replication of HIV-1. Actin polymerization mediated by the Arp2/3 complex has been found to play a critical role in some pathogens' intracellular motility. We have asked whether this complex also contributes to the viral life cycles including that of HIV-1. We have used both the acidic domains from actin-related protein (Arp) 2/3 complex-binding proteins such as the Wiscott-Aldrich syndrome protein (N-WASP) or cortactin, and siRNA directing toward Arp2 to inhibit viral infection. HIV-1, simian immunodeficiency virus (SIV), and intracellular mature vaccinia virus (IMV) were sensitive to inhibition of the Arp2/3 complex, whereas MLV, HSV-1, and adenovirus were not. Interestingly, pseudotyping HIV-1 with vesicular stomatitis virus G protein (VSV-G) overcame this inhibition. Constitutive inhibition of the Arp2/3 complex in the T-cell line H9 also blocked replication of HIV-1. These data suggested the existence of an Arp2/3 complex-dependent event during the early phase of the life cycles of both primate lentiviruses and IMV. Inhibiting the HIV-1's ability to activate Arp2/3 complex could be a potential chemotherapeutic intervention for acquired immunodeficiency syndrome (AIDS).
Komano
Jun
J
Laboratory of Virology and Pathogenesis, AIDS Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan. ajkomano@nih.go.jp
Miyauchi
Kosuke
K
Matsuda
Zene
Z
Yamamoto
Naoki
N
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D042541:Intracellular Space / Q000821:virology*; D017958:Lentiviruses, Primate / Q000502:physiology*; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014616:Vaccinia virus / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D003598:Cytoskeletal Proteins; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D014759:Viral Envelope Proteins; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal