Neutralizing antibody blocks adenovirus infection by arresting microtubule-dependent cytoplasmic transport.
Neutralizing antibodies are commonly elicited by viral infection. Most antibodies that have been characterized block early stages of virus entry that occur before membrane penetration, whereas inhibition of late stages in entry that occurs after membrane penetration has been poorly characterized. Here we provide evidence that the neutralizing antihexon monoclonal antibody 9C12 inhibits adenovirus infection by blocking microtubule-dependent translocation of the virus to the microtubule-organizing center following endosome penetration. These studies identify a previously undescribed mechanism by which neutralizing antibodies block virus infection, a situation that may be relevant for other nonenveloped viruses that use microtubule-dependent transport during cell entry.
Smith
Jason G
JG
Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Cassany
Aurelia
A
Gerace
Larry
L
Ralston
Robert
R
Nemerow
Glen R
GR
D000258:Adenovirus Infections, Human / Q000276:immunology / Q000503:physiopathology*; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology; D036022:Capsid Proteins / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D028961:beta Karyopherins / Q000302:isolation & purification / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D028961:beta Karyopherins; C018315:hexon capsid protein, Adenovirus