Involvement of cytoskeletal components in BK virus infectious entry.
Posttransplant reactivation of BK virus (BKV) in the renal allograft progresses to polyomavirus-associated nephropathy in 1% to 8% of kidney recipients. Graft dysfunction and loss in 30% to 45% of polyomavirus-associated nephropathy-affected patients are secondary to extensive tubular epithelial cell injury induced by the lytic replication of BKV. The early events in productive BKV infection are not thoroughly understood. We have previously shown that BKV enters cells by caveola-mediated endocytosis. In this report we examine the role of microfilaments and microtubules during early viral infection. Our results show that BKV infection of Vero cells is sensitive to nocodazole-induced disassembly of the microtubule network for the initial 8 hours following virus binding. In contrast, suppression of microtubule turnover with the stabilizing agent paclitaxel has no effect on BKV infectivity. Selective disassembly of the actin filaments with latrunculin A does not impede BKV infection, while inhibition of microfilament dynamics with jasplakinolide results in reduced numbers of viral antigen-positive cells. These data demonstrate that BKV, like other polyomaviruses, relies on an intact microtubule network during early infection. BKV, however, does not share the requirement with the closely related JC virus for an intact actin cytoskeleton during intracellular transport.
Eash
Sylvia
S
Graduate Program in Pathobiology, Brown University, 70 Ship Street, Providence, RI 02903, USA.
Atwood
Walter J
WJ
D000199:Actins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001739:BK Virus / Q000472:pathogenicity*; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism / Q000821:virology*; D047630:Depsipeptides / Q000494:pharmacology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D007700:Kinetics; D008870:Microtubules / Q000187:drug effects / Q000821:virology; D015739:Nocodazole / Q000494:pharmacology; D027601:Polyomavirus Infections / Q000209:etiology* / Q000378:metabolism / Q000821:virology; D014412:Tumor Virus Infections / Q000209:etiology* / Q000378:metabolism / Q000821:virology; D014709:Vero Cells
D000199:Actins; D047630:Depsipeptides; C057531:jasplakinolide; D015739:Nocodazole