Identification of a dynein interacting domain in the papillomavirus minor capsid protein l2.
Papillomaviruses enter cells via endocytosis (H. C. Selinka et al., Virology 299:279-287, 2002). After egress from endosomes, the minor capsid protein L2 accompanies the viral DNA to the nucleus and subsequently to the subnuclear promyelocytic leukemia protein bodies (P. M. Day et al., Proc. Natl. Acad. Sci. USA 101:14252-14257, 2004), suggesting that this protein may be involved in the intracytoplasmic transport of the viral genome. We now demonstrate that the L2 protein is able to interact with the microtubule network via the motor protein dynein. L2 protein was found attached to microtubules after uncoating of incoming human papillomavirus pseudovirions. Based on immunofluorescence and coimmunoprecipitation analyses, the L2 region interacting with dynein is mapped to the C-terminal 40 amino acids. Mutations within this region abrogating the L2/dynein interaction strongly reduce the infectivity of pseudoviruses, indicating that this interaction mediates the minus-end-directed transport of the viral genome along microtubules towards the nucleus.
Florin
Luise
L
Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Becker
Katrin A
KA
Lambert
Carsten
C
Nowak
Thorsten
T
Sapp
Cornelia
C
Strand
Dennis
D
Streeck
Rolf E
RE
Sapp
Martin
M
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism* / Q000821:virology; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding
D036022:Capsid Proteins; D004279:DNA, Viral; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; C080100:oncogene viral capsid protein L2, human papillomavirus type 33; D004398:Dyneins