Search results for "Viral Entry"

Cytoplasmic Parvovirus Capsids Recruit Importin Beta for Nuclear Delivery

2019

Parvoviruses are an important platform for gene and cancer therapy. Their cell entry and the following steps, including nuclear import, are inefficient, limiting their use in therapeutic applications. Two models exist on parvoviral nuclear entry: the classical import of the viral capsid using nuclear transport receptors of the importin (karyopherin) family or the direct attachment of the capsid to the nuclear pore complex leading to the local disintegration of the nuclear envelope. Here, by laser scanning confocal microscopy and in situ proximity ligation analyses combined with coimmunoprecipitation, we show that infection requires importin β-mediated access to the nuclear pore complex and …

Towards therapeutic gene delivery to human cancer cells : targeting and entry of baculovirus

2008

Geeniterapia on yksi tulevaisuuden hoitomuodoista taistelussa syöpää vastaan. Virukset ovat evoluution myötä kehittyneet tehokkaiksi geeninsiirtäjiksi ja ovat nykyään käytetyimpiä geeninsiirtovektoreita. Yksi geenihoitojen yleistymisen esteistä on kuitenkin ollut virusvektoreiden puutteellinen kohdennus haluttuun kudokseen. Kohdentaminen on erityisen tärkeää syövän hoidossa, jotta hoito vaikuttaisi pääasiassa pahanlaatuisiin soluihin.Mäkelä kehitti tutkimuksessaan syöpäsoluihin kohdentuvia bakulovirusperäisiä geeninsiirtovektoreita. Hän tutki myös viruksen sisäänmenomekanismeja ja kulkeutumista kohdesoluissa.- Hyönteisiä infektoiva bakulovirus on luontaisesti vaaraton ihmisille. Se on helpo…

2014

Human papillomaviruses (HPV) are non-enveloped DNA tumor viruses that infect skin and mucosa. The most oncogenic subtype, HPV16, causes various types of cancer, including cervical, anal, and head and neck cancers. During the multistep process of infection, numerous host proteins are required for the delivery of virus genetic information into the nucleus of target cells. Over the last two decades, many host-cell proteins such as heparan sulfate proteoglycans, integrins, growth factor receptors, actin and the tetraspanin CD151 have been described to be involved in the process of infectious entry of HPV16. Tetraspanins have the ability to organize membrane microdomains and to directly influenc…

Peptide-mediated interference with baculovirus transduction

2007

Baculovirus represents a multifunctional platform with potential for biomedical applications including disease therapies. The importance of F3, a tumor-homing peptide, in baculovirus transduction was previously recognized by the ability of F3 to augment viral binding and gene delivery to human cancer cells following display on the viral envelope. Here, F3 was utilized as a molecular tool to expand understanding of the poorly characterized baculovirus-mammalian cell interactions. Baculovirus-mediated transduction of HepG2 hepatocarcinoma cells was strongly inhibited by coincubating the virus with synthetic F3 or following incorporation of F3 into viral nucleocapsid by genetic engineering, th…

Baculovirus-mediated immediate-early gene expression and nuclear reorganization in human cells

2007

Baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), has the ability to transduce mammalian cell lines without replication. The general objective of this study was to detect the transcription and expression of viral immediate-early genes in human cells and to examine the interactions between viral components and subnuclear structures. Viral capsids were seen in large, discrete foci in nuclei of both dividing and non-dividing human cells. Concurrently, the transcription of viral immediate-early transregulator genes (ie-1, ie-2) and translation of IE-2 protein were detected. Quantitative microscopy imaging and analysis showed that virus transduction altered the size of …

The Extracellular δ-Domain is Essential for the Formation of CD81 Tetraspanin Webs

2014

AbstractCD81 is a ubiquitously expressed member of the tetraspanin family. It forms large molecular platforms, so-called tetraspanin webs that play physiological roles in a variety of cellular functions and are involved in viral and parasite infections. We have investigated which part of the CD81 molecule is required for the formation of domains in the cell membranes of T-cells and hepatocytes. Surprisingly, we find that large CD81 platforms assemble via the short extracellular δ-domain, independent from a strong primary partner binding and from weak interactions mediated by palmitoylation. The δ-domain is also essential for the platforms to function during viral entry. We propose that, ins…