HPV16 and BPV1 infection can be blocked by the dynamin inhibitor dynasore.
The initial entry of papillomaviruses into their target cells has been shown to occur by clathrin-mediated endocytosis and caveolae-mediated endocytosis. These mechanisms entail the formation of nascent-coated vesicles at the plasma membrane. Such coated vesicles, clathrin or caveolin, form and pinch-off in a controlled mechanism that involves several proteins including dynamin. Dynamin is a GTPase that forms a dynamin ring at the stem connecting the nascent vesicle to the plasma membrane. In a still not fully characterized mechanism, dynamin's contraction and twisting results in the scission of the vesicle. In an effort to better characterize the role and molecular mechanisms of dynamin's function, researchers have identified dynasore, a dynamin GTPase inhibitor that prevents the scission of dynamin-dependent endocytic vesicles. Here, we have tested if infection by pseudovirus corresponding to the oncogenic human papillomavirus type 16 and bovine papillomavirus type 1 can be blocked by dynasore. We present data demonstrating that dynasore can block infection of human papillomavirus type 16 and bovine papillomavirus type 1 pseudovirions in a dose- and time-dependent manner with equal efficiency. Presently, there is no available therapy that can block infection by a wide range of papillomavirus regardless of species or genotypes. Targeting dynamin may lead to the rational design of drug able to prevent infection by papillomaviruses, and by other infectious agents dependent on this protein for initial internalization into target cells. Whether such an approach will prove successful needs further investigation.
Abban
Cynthia Y
CY
School of Graduate and Postdoctoral Studies, H. M. Bligh Cancer Research Laboratory, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Bradbury
Neil A
NA
Meneses
Patricio I
PI
D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D052688:Bovine papillomavirus 1 / Q000187:drug effects* / Q000472:pathogenicity; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D034281:Dynamins / Q000037:antagonists & inhibitors*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D052162:Human papillomavirus 16 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000998:Antiviral Agents; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D020558:GTP Phosphohydrolases; D034281:Dynamins