Protoparvovirus Cell Entry

Abstract

The Protoparvovirus (PtPV) genus of the Parvoviridae family of viruses includes important animal pathogens and reference molecular models for the entire family. Some virus members of the PtPV genus have arisen as promising tools to treat tumoral processes, as they exhibit marked oncotropism and oncolytic activities while being nonpathogenic for humans. The PtPVs invade and replicate within the nucleus making extensive use of the transport, transcription and replication machineries of the host cells. In order to reach the nucleus, PtPVs need to cross over several intracellular barriers and traffic through different cell compartments, which limit their infection efficiency. In this review we summarize molecular interactions, capsid structural transitions and hijacking of cellular processes, by which the PtPVs enter and deliver their single-stranded DNA genome into the host cell nucleus. Understanding mechanisms that govern the complex PtPV entry will be instrumental in developing approaches to boost their anticancer therapeutic potential and improving their safety profile.

Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis

“…Previous research has reported that other PtPVs use clathrin-mediated endocytosis to gain access to cells and progress the infection (reviewed in Reference [ 3 ]). Our results are therefore in agreement with the idea that clathrin-mediated endocytosis is the default entry pathway for PtPVs.…”

“…The rodent H-1 protoparvovirus (H-1PV) belongs to the Parvoviridae family, genus Protoparvovirus [ 1 ]. This genus also includes Rodent protoparvovirus 1 (H-1PV, Kilham rat virus, LuIII virus, minute virus of mice (MVM), mouse parvovirus, tumour virus X, rat minute virus), Rodent protoparvovirus 2 (rat parvovirus 1), Carnivore protoparvovirus 1 (canine parvovirus (CPV) and feline panleukopenia parvovirus (FPV)), Primate protoparvovirus 1 (bufavirus) and Ungulate parvovirus 1 (porcine parvovirus (PPV)) [ 2 , 3 ]. Protoparvoviruses (PtPVs) are single-stranded DNA viruses with an icosahedral capsid of about 25 nm diameter.…”

“…H-1PV, like MVM and PPV, uses sialic acid (SA) for cell surface attachment and entry. However, it is unclear whether SA itself acts as a functional viral receptor for the virus or is a component of an as yet unidentified receptor(s) or receptor complex [ 3 , 11 , 12 ].…”

“…In particular, the acidic environment exposes the catalytic phospholipase 2 domain of VP1. This conformational change promotes the digestion of the endosomal membrane, resulting in the release of viral particles from the late endosome to the cytosol [ 3 ]. Thereafter, incoming PtPV particles are transported to the nucleus in a process that is dependent on the cytoskeleton and associated motor proteins [ 23 ].…”

Structural determinants of mechanical resistance against breakage of a virus-based protein nanoparticle at a resolution of single amino acids

“…[45][46][47][48][49][50] A particularly suited model for these studies is the icosahedral capsid of the minute virus of mice (MVM). 51,52 The MVM capsid ( Fig. 1A and B), one of the smallest (25 nm in diameter) and structurally simplest viral NPs known, is made of a minimum number (60) of structurally equivalent protein monomers that have the same sequence and fold.…”