0000000000498291
AUTHOR
Sanna Suikkanen
Exploitation of Microtubule Cytoskeleton and Dynein during Parvoviral Traffic toward the Nucleus
ABSTRACT Canine parvovirus (CPV), a model virus for the study of parvoviral entry, enters host cells by receptor-mediated endocytosis, escapes from endosomal vesicles to the cytosol, and then replicates in the nucleus. We examined the role of the microtubule (MT)-mediated cytoplasmic trafficking of viral particles toward the nucleus. Immunofluorescence and immunoelectron microscopy showed that capsids were transported through the cytoplasm into the nucleus after cytoplasmic microinjection but that in the presence of MT-depolymerizing agents, viral capsids were unable to reach the nucleus. The nuclear accumulation of capsids was also reduced by microinjection of an anti-dynein antibody. More…
Cell biology of canine parvovirus entry
Sanna Suikkasen väitöskirjatyössä havaittiin, että koiran parvovirus tarvitsee solun tarjoamaa kuljetuskoneistoa edetäkseen sen sisällä ja happamia olosuhteita pystyäkseen lisääntymään. Tulokset antavat kehykset viruksen ja sen läheisten sukulaisten solunsisäisen reitin tarkemmalle tutkimukselle ja luovat pohjaa viruslääkkeiden suunnitteluun. Mielenkiintoa parvoviruksien tutkimukseen lisää tutkijan mielestä myös kiinnostus parvopartikkeleiden geeniterapiasovellutuksiin. Koiran parvovirus eriytyi kissan panleukopeniaviruksesta 1970-luvun lopulla ja levisi nopeasti ympäri maailmaa. Se aiheuttaa aikuisille koirille ankaraa ripulia ja pennuille tappavia sydänlihastulehduksia. Parvovirukset aihe…
Release of canine parvovirus from endocytic vesicles
Canine parvovirus (CPV) is a small nonenveloped virus with a single-stranded DNA genome. CPV enters cells by clathrin-mediated endocytosis and requires an acidic endosomal step for productive infection. Virion contains a potential nuclear localization signal as well as a phospholipase A(2) like domain in N-terminus of VP1. In this study we characterized the role of PLA(2) activity on CPV entry process. PLA(2) activity of CPV capsids was triggered in vitro by heat or acidic pH. PLA(2) inhibitors inhibited the viral proliferation suggesting that PLA(2) activity is needed for productive infection. The N-terminus of VP1 was exposed during the entry, suggesting that PLA(2) activity might have a …
Pathways of Cell Infection by Parvoviruses and Adeno-Associated Viruses
Animal viruses have developed various strategies for infecting cells, and all begin with adsorption to cell surface receptors, penetration into the cytosol, uncoating or release of the viral genome, and targeting the genome and any required accessory proteins toward the correct cellular organelle or compartment for replication (26, 48, 63). Since genome delivery and release require the rearrangement of the viral structures, infection is normally a multistep process involving various viral and cellular components. Viruses that replicate in the nucleus must have mechanisms for transporting the genome and other components to the vicinity of the nuclear pore and into the nucleus (84). The endos…
Improvement in Nuclear Entry and Transgene Expression of Baculoviruses by Disintegration of Microtubules in Human Hepatocytes
ABSTRACT Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), a potent virus for mammalian cell gene delivery, possesses an ability to transduce mammalian cells without viral replication. We examined the role of the cellular cytoskeleton in the cytoplasmic trafficking of viral particles toward the nucleus in human hepatic cells. Microscopic studies showed that capsids were found in the nucleus after either viral inoculation or cytoplasmic microinjection of nucleocapsids. The presence of microtubule (MT) depolymerizing agents caused the amount of nuclear capsids to increase. Overexpression of p50/dynamitin, an inhibitor of dynein-dependent endocytic trafficking from peripheral e…
Role of Recycling Endosomes and Lysosomes in Dynein-Dependent Entry of Canine Parvovirus
ABSTRACT Canine parvovirus (CPV) is a nonenveloped virus with a 5-kb single-stranded DNA genome. Lysosomotropic agents and low temperature are known to prevent CPV infection, indicating that the virus enters its host cells by endocytosis and requires an acidic intracellular compartment for penetration into the cytoplasm. After escape from the endocytotic vesicles, CPV is transported to the nucleus for replication. In the present study the intracellular entry pathway of the canine parvovirus in NLFK (Nordisk Laboratory feline kidney) cells was studied. After clustering in clathrin-coated pits and being taken up in coated vesicles, CPV colocalized with coendocytosed transferrin in endosomes r…