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Vol. 15, Issue 12, 5197-5207, December 2004

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Inhibiting the Arp2/3 Complex Limits Infection of Both Intracellular Mature Vaccinia Virus and Primate Lentiviruses

Laboratory of Virology and Pathogenesis, AIDS Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan

Submitted April 2, 2004; Revised September 6, 2004; Accepted September 13, 2004
Monitoring Editor: Thomas Pollard

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).

Abbreviations used: Arp2/3, actin-related protein 2/3; CC, cytochalasin; GFP, green fluorescent protein; HIV-1, human immunodeficiency virus type 1; HSV-1, herpes simplex virus type 1; IMV, intracellular mature virus; MLV, murine leukemia virus; RLU, relative light unit; SIV, simian immunodeficiency virus; VSV-G, vesicular stomatitis virus G protein; VV, vaccinia virus; WASP, Wiscott-Aldrich syndrome protein.

^* Corresponding author. E-mail address: ajkomano{at}nih.go.jp.

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