Coat as a Dagger: The Use of Capsid Proteins to Perforate Membranes during Non-Enveloped DNA Viruses Trafficking

Bílková, Eva; Forstová, Jitka; Abrahamyan, Levon

doi:10.3390/v6072899

Cited by 15 publications

(16 citation statements)

References 235 publications

(333 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Not surprisingly, other nonenveloped DNA viruses also must utilize membrane translocation (61). After endocytic uptake, simian virus 40 (SV40) is trafficked to the ER, whereupon the virion uncoats and undergoes conformational changes leading to the exposure of VP2.…”

Section: Discussionmentioning

confidence: 99%

Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry

DiGiuseppe

Keiffer

Bienkowska-Haba

et al. 2015

J Virol

View full text Add to dashboard Cite

The human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to the trans-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors. These data imply that a portion of L2 becomes cytosolic during infection. Using a low concentration of digitonin to selectively permeabilize the plasma membrane of infected cells, we mapped the topography of the L2 protein during infection. We observed that epitopes within amino acid residues 64 to 81 and 163 to 170 and a C-terminal tag of HPV16 L2 are exposed on the cytosolic side of intracellular membranes, whereas an epitope within residues 20 to 38, which are upstream of a putative transmembrane region, is luminal. Corroborating these findings, we also found that L2 protein is sensitive to trypsin digestion during infection. These data demonstrate that the majority of the L2 protein becomes accessible on the cytosolic side of intracellular membranes in order to interact with cytosolic factors to facilitate vesicular trafficking. IMPORTANCEIn order to complete infectious entry, nonenveloped viruses have to pass cellular membranes. This is often achieved through the viral capsid protein associating with or integrating into intracellular membrane. Here, we determine the topography of HPV L2 protein in the endocytic vesicular compartment, suggesting that L2 becomes a transmembrane protein with a short luminal portion and with the majority facing the cytosolic side for interaction with host cell transport factors. Human papillomaviruses (HPVs) are nonenveloped DNA tumor viruses that infect the skin and mucosal epithelial cells. Infection by HPVs can induce hyper-proliferative lesions of the tissues, whereupon high-risk HPVs can progress to malignant tumors. Of the high-risk HPVs, 70% of cervical cancer can be attributed to HPVs 16 and 18 (1). These HPVs are associated with a variety of anogenital and oral carcinomas. Despite the success of the prophylactic vaccine against these high-risk HPVs, HPV-associated cancers will continue to be a global health burden in the future due to low vaccination rates and lack of therapeutic effect (2). Therefore, uncovering the conserved steps of how HPVs establish infection can be used to find antiviral targets that may be less virus restrictive than the current vaccines.The HPV capsid is composed of 360 molecules of the major capsid protein, L1, and up to 72 molecules of the minor capsid protein, L2 (3-6). Much of our advancement in understanding HPV entry can be attributed to the efficient generation of pseudovirions. With respect to cellular entry, pseudovirions are considered to be indistinguishable from native virions but encapsidate a reporter plasmid (pseudogenome) in place of the HP...

show abstract

Section: Discussionmentioning

confidence: 99%

Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry

DiGiuseppe

Keiffer

Bienkowska-Haba

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…Many factors are known to affect susceptibility of the cells to viral invasion. For example, host antiviral restriction factors induce cellular resistance against a number of viral pathogens (Kluge et al 2015), and capsid proteins of small non-enveloped DNA viruses play an important role in intracellular membrane perturbation in the early stages of viral infection (Bilkova et al 2014). Therefore, identifying the key determinants influencing the susceptibility of cells to different viruses, as classified by the Baltimore system, is of the utmost importance.…”

Section: Introductionmentioning

confidence: 99%

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

Dai

Zhang

Ostrikov

et al. 2020

Critical Reviews in Microbiology

Self Cite

View full text Add to dashboard Cite

Cell culture-based vaccine technology is a flexible and convenient approach for vaccine production that requires adaptation of the vaccine strains to the new cells. Driven by the motivation to develop a broadly permissive cell line for infection with a wide range of viruses, we identified a set of the most relevant host receptors involved in viral attachment and entry. This identification was done through a review of different viral entry pathways and host cell lines, and in the context of the Baltimore classification of viruses. In addition, we indicated the potential technical problems and proposed some solutions regarding how to modify the host cell genome in order to meet industrial requirements for mass production of antiviral vaccines. Our work contributes to a finer understanding of the importance of breaking the host-virus recognition specificities for the possibility of creating a cell line feasible for the production of vaccines against a broad spectrum of viruses. ARTICLE HISTORY

show abstract

“…A possible explanation could be related to the idiosyncrasy of tospovirus infecting plant and insect organisms. In addition to virus particle, the capability to transport NPC between cells has been reported only for plant viruses meanwhile virions is a prerequisite for animal or insect virus transport (Bilkova et al, 2014;Kilcher and Mercer, 2015;Marsh and Helenius, 2006). In this sense, we can hypothesize that the NS M of tospovirus have evolved to transport only nucleoprotein complexes that is compatible both plant and insect organism.…”

Section: Discussionmentioning

confidence: 99%

The functional analysis of distinct tospovirus movement proteins (NS M ) reveals different capabilities in tubule formation, cell-to-cell and systemic virus movement among the tospovirus species

et al. 2017

View full text Add to dashboard Cite

The lack of infectious tospovirus clones to address reverse genetic experiments has compromised the functional analysis of viral proteins. In the present study we have performed a functional analysis of the movement proteins (NS) of four tospovirus species Bean necrotic mosaic virus (BeNMV), Chrysanthemum stem necrosis virus (CSNV), Tomato chlorotic spot virus (TCSV) and Tomato spotted wilt virus (TSWV), which differ biologically and molecularly, by using the Alfalfa mosaic virus (AMV) model system. All NS proteins were competent to: i) support the cell-to-cell and systemic transport of AMV, ii) generate tubular structures on infected protoplast and iii) transport only virus particles. However, the NS of BeNMV (one of the most phylogenetically distant species) was very inefficient to support the systemic transport. Deletion assays revealed that the C-terminal region of the BeNMV NS, but not that of the CSNV, TCSV and TSWV NS proteins, was dispensable for cell-to-cell transport, and that all the non-functional C-terminal NS mutants were unable to generate tubular structures. Bimolecular fluorescence complementation analysis revealed that the C-terminus of the BeNMV NS was not required for the interaction with the cognate nucleocapsid protein, showing a different protein organization when compared with other movement proteins of the '30K family'. Overall, our results revealed clearly differences in functional aspects among movement proteins from divergent tospovirus species that have a distinct biological behavior.

show abstract

Coat as a Dagger: The Use of Capsid Proteins to Perforate Membranes during Non-Enveloped DNA Viruses Trafficking

Cited by 15 publications

References 235 publications

Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry

Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

The functional analysis of distinct tospovirus movement proteins (NS M ) reveals different capabilities in tubule formation, cell-to-cell and systemic virus movement among the tospovirus species

Contact Info

Product

Resources

About