scholarly journals SV40 Hijacks Cellular Transport, Membrane Penetration, and Disassembly Machineries to Promote Infection

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 917 ◽  
Author(s):  
Chen ◽  
Liu ◽  
Tsai
Keyword(s):  
Host Cell ◽  
Membrane Transport ◽  
Current Model ◽  
Cellular Membrane ◽  
Cellular Transport ◽  
Endomembrane System ◽  
Virus Family ◽  
Nonenveloped Virus ◽  
Infectious Entry ◽  
Do So

During entry, a virus must be transported through the endomembrane system of the host cell, penetrate a cellular membrane, and undergo capsid disassembly, to reach the cytosol and often the nucleus in order to cause infection. To do so requires the virus to coordinately exploit the action of cellular membrane transport, penetration, and disassembly machineries. How this is accomplished remains enigmatic for many viruses, especially for viruses belonging to the nonenveloped virus family. In this review, we present the current model describing infectious entry of the nonenveloped polyomavirus (PyV) SV40. Insights from SV40 entry are likely to provide strategies to combat PyV-induced diseases, and to illuminate cellular trafficking, membrane transport, and disassembly mechanisms.

scholarly journals A Functional Interaction between Herpes Simplex Virus 1 Glycoprotein gH/gL Domains I and II and gD Is Defined by Using Alphaherpesvirus gH and gL Chimeras

2015 ◽  
Vol 89 (14) ◽  
pp. 7159-7169 ◽  
Author(s):  
Qing Fan ◽  
Richard Longnecker ◽  
Sarah A. Connolly
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Current Model ◽  
Viral Envelope ◽  
Functional Interaction ◽  
Herpes Simplex Virus 1 ◽  
Homotypic Interaction ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTWhereas most viruses require only a single protein to bind to and fuse with cells, herpesviruses use multiple glycoproteins to mediate virus entry, and thus communication among these proteins is required. For most alphaherpesviruses, the minimal set of viral proteins required for fusion with the host cell includes glycoproteins gD, gB, and a gH/gL heterodimer. In the current model of entry, gD binds to a cellular receptor and transmits a signal to gH/gL. This signal then triggers gB, the conserved fusion protein, to insert into the target membrane and refold to merge the viral and cellular membranes. We previously demonstrated that gB homologs from two alphaherpesviruses, herpes simplex virus 1 (HSV-1) and saimiriine herpesvirus 1 (SaHV-1), were interchangeable. In contrast, neither gD nor gH/gL functioned with heterotypic entry glycoproteins, indicating that gD and gH/gL exhibit an essential type-specific functional interaction. To map this homotypic interaction site on gH/gL, we generated HSV-1/SaHV-1 gH and gL chimeras. The functional interaction with HSV-1 gD mapped to the N-terminal domains I and II of the HSV-1 gH ectodomain. The core of HSV-1 gL that interacts with gH also was required for functional homotypic interaction. The N-terminal gH/gL domains I and II are the least conserved and may have evolved to support species-specific glycoprotein interactions.IMPORTANCEThe first step of the herpesvirus life cycle is entry into a host cell. A coordinated interaction among multiple viral glycoproteins is required to mediate fusion of the viral envelope with the cell membrane. The details of how these glycoproteins interact to trigger fusion are unclear. By swapping the entry glycoproteins of two alphaherpesviruses (HSV-1 and SaHV-1), we previously demonstrated a functional homotypic interaction between gD and gH/gL. To define the gH and gL requirements for homotypic interaction, we evaluated the function of a panel of HSV-1/SaHV-1 gH and gL chimeras. We demonstrate that domains I and II of HSV-1 gH are sufficient to promote a functional, albeit reduced, interaction with HSV-1 gD. These findings contribute to our model of how the entry glycoproteins cooperate to mediate herpesvirus entry into the cell.

scholarly journals Reassessing the mechanics of parasite motility and host-cell invasion

2016 ◽  
Vol 214 (5) ◽  
pp. 507-515 ◽  
Author(s):  
Isabelle Tardieux ◽  
Jake Baum
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Cell Invasion ◽  
Motor System ◽  
Current Model ◽  
Cell Movement ◽  
Host Cell Invasion ◽  
Motor Functions ◽  
Apicomplexan Parasites ◽  
Parasite Motility

The capacity to migrate is fundamental to multicellular and single-celled life. Apicomplexan parasites, an ancient protozoan clade that includes malaria parasites (Plasmodium) and Toxoplasma, achieve remarkable speeds of directional cell movement. This rapidity is achieved via a divergent actomyosin motor system, housed within a narrow compartment that lies underneath the length of the parasite plasma membrane. How this motor functions at a mechanistic level during motility and host cell invasion is a matter of debate. Here, we integrate old and new insights toward refining the current model for the function of this motor with the aim of revitalizing interest in the mechanics of how these deadly pathogens move.

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

2015 ◽  
Vol 89 (20) ◽  
pp. 10442-10452 ◽  
Author(s):  
Stephen DiGiuseppe ◽  
Timothy R. Keiffer ◽  
Malgorzata Bienkowska-Haba ◽  
Wioleta Luszczek ◽  
Lucile G. M. Guion ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Host Cell ◽  
Capsid Protein ◽  
Conformational Changes ◽  
Transmembrane Protein ◽  
Vesicular Trafficking ◽  
Minor Capsid Protein ◽  
Intracellular Membranes ◽  
Cytosolic Side ◽  
Infectious Entry

ABSTRACTThe 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 thetrans-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.

scholarly journals The Small-Compound Inhibitor K22 Displays Broad Antiviral Activity against Different Members of the Family Flaviviridae and Offers Potential as a Panviral Inhibitor

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Obdulio García-Nicolás ◽  
Philip V'kovski ◽  
Nathalie J. Vielle ◽  
Nadine Ebert ◽  
Roland Züst ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Host Cell ◽  
Rna Viruses ◽  
Close Association ◽  
Viral Inhibition ◽  
Virus Family ◽  
Positive Strand ◽  
Content Type ◽  
Small Compound ◽  
Positive Strand Rna

ABSTRACT The virus family Flaviviridae encompasses several viruses, including (re)emerging viruses which cause widespread morbidity and mortality throughout the world. Members of this virus family are positive-strand RNA viruses and replicate their genome in close association with reorganized intracellular host cell membrane compartments. This evolutionarily conserved strategy facilitates efficient viral genome replication and contributes to evasion from host cell cytosolic defense mechanisms. We have previously described the identification of a small-compound inhibitor, K22, which exerts a potent antiviral activity against a broad range of coronaviruses by targeting membrane-bound viral RNA replication. To analyze the antiviral spectrum of this inhibitor, we assessed the inhibitory potential of K22 against several members of the Flaviviridae family, including the reemerging Zika virus (ZIKV). We show that ZIKV is strongly affected by K22. Time-of-addition experiments revealed that K22 acts during a postentry phase of the ZIKV life cycle, and combination regimens of K22 together with ribavirin (RBV) or interferon alpha (IFN-α) further increased the extent of viral inhibition. Ultrastructural electron microscopy studies revealed severe alterations of ZIKV-induced intracellular replication compartments upon infection of K22-treated cells. Importantly, the antiviral activity of K22 was demonstrated against several other members of the Flaviviridae family. It is tempting to speculate that K22 exerts its broad antiviral activity against several positive-strand RNA viruses via a similar mechanism and thereby represents an attractive candidate for development as a panviral inhibitor.

Targeting of host-cell ubiquitin pathways by viruses

2005 ◽  
Vol 41 ◽  
pp. 139-156 ◽  
Author(s):  
Julia Shackelford ◽  
Joseph S. Pagano
Keyword(s):  
Host Cell ◽  
Cell Biology ◽  
Cell Signalling ◽  
Ubiquitin Proteasome System ◽  
Life Cycles ◽  
Therapeutic Interventions ◽  
Signalling Pathways ◽  
Cellular Functions ◽  
Ubiquitin Proteasome ◽  
Do So

The ability of viruses to co-opt cell signalling pathways has, over millions of years of co-evolution, come to pervade nearly every facet of cellular functions. Recognition of the extent to which the ubiquitin–proteasome system can be directed or subverted by viruses is relatively recent. Viral products interact with, and adjust, the ubiquitin–proteasome machinery precisely and at many levels, and they do so at distinct stages of viral life-cycles. The implications for both cells and viruses are fundamental, and understanding viral strategies in this context opens up fascinating new areas for research that span from basic cell biology to therapeutic interventions against both viruses and malignancies.

2-Fluoroadenosine uptake by erythrocytes and endothelial cells studied by 19F-NMR

1994 ◽  
Vol 266 (4) ◽  
pp. H1596-H1603 ◽  
Author(s):  
U. K. Decking ◽  
C. Alves ◽  
R. Spahr ◽  
J. Schrader
Keyword(s):  
Endothelial Cells ◽  
Chemical Shift ◽  
Membrane Transport ◽  
Time Course ◽  
Adenosine Kinase ◽  
19F Nmr ◽  
Cellular Transport ◽  
Aortic Endothelial Cells ◽  
Porcine Aortic Endothelial Cells ◽  
Aortic Endothelial

Transport and phosphorylation of 2-fluoroadenosine (F-AR) were studied in human erythrocytes and porcine aortic endothelial cells by 19F-nuclear magnetic resonance (NMR) spectroscopy. F-AR (590 microM) added to a human erythrocyte suspension (15% hematocrit) was rapidly incorporated into adenine nucleotides at a rate of 38 nmol.min-1.ml red blood cells-1. Intracellular F-AR could be distinguished from extracellular F-AR due to a chemical shift difference of 0.43 +/- 0.03 ppm (n = 5 experiments). Compared with F-AR, fluoro-ATP purified by high-performance liquid chromatography (HPLC) exhibited a chemical shift of -0.052 ppm, which was too small to differentiate intracellular F-AR and fluoro-ATP in vivo. F-AR uptake was decreased by inhibition of membrane transport with dipyridamole (25 microM) or blockade of adenosine kinase by iodotubercidin (10 microM). The time course of F-AR uptake suggested that the rate-limiting step was not membrane transport but the intracellular phosphorylation by adenosine kinase. In porcine aortic endothelial cells grown on microcarrier beads and perfused within the magnet, there was a linear relation between the F-AR concentration applied (2, 4, 8, or 32 microM) and net uptake measured (27-827 pmol.min-1.mg-1). Intra- and extracellular fluoroadenine compounds were separated by 0.12 ppm, and HPLC analysis confirmed F-AR conversion to fluoroadenine nucleotides. Our findings demonstrate that cellular transport and metabolism of F-AR can be noninvasively studied and analyzed by 19F-NMR.

scholarly journals Inhibiting fusion with cellular membrane system: therapeutic options to prevent severe acute respiratory syndrome coronavirus-2 infection

2020 ◽  
Vol 319 (3) ◽  
pp. C500-C509
Author(s):  
Prasenjit Mitra
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Host Cell ◽  
Membrane System ◽  
Cell Receptor ◽  
Cellular Membrane ◽  
Therapeutic Options ◽  
Viral Fusion ◽  
Enveloped Virus ◽  
Host Cell Receptor ◽  
Endogenous Proteases

Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped virus with a positive-sense single-stranded RNA genome, facilitates the host cell entry through intricate interactions with proteins and lipids of the cell membrane. The detailed molecular mechanism involves binding to the host cell receptor and fusion at the plasma membrane or after being trafficked to late endosomes under favorable environmental conditions. A crucial event in the process is the proteolytic cleavage of the viral spike protein by the host’s endogenous proteases that releases the fusion peptide enabling fusion with the host cellular membrane system. The present review details the mechanism of viral fusion with the host and highlights the therapeutic options that prevent SARS-CoV-2 entry in humans.

scholarly journals pilQ Missense Mutations Have Diverse Effects on PilQ Multimer Formation, Piliation, and Pilus Function in Neisseria gonorrhoeae

2007 ◽  
Vol 189 (8) ◽  
pp. 3198-3207 ◽  
Author(s):  
R. Allen Helm ◽  
Michelle M. Barnhart ◽  
H. Steven Seifert
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Host Cell ◽  
Current Model ◽  
Active Role ◽  
Colony Morphology ◽  
Single Amino Acid ◽  
Missense Mutations ◽  
Cell Adherence ◽  
Type Iv ◽  
Host Epithelium

ABSTRACT Type IV pili are required for virulence in Neisseria gonorrhoeae, as they are involved in adherence to host epithelium, twitching motility, and DNA transformation. The outer membrane secretin PilQ forms a homododecameric ring through which the pilus is proposed to be secreted. pilQ null mutants are nonpiliated, and thus, all pilus-dependent functions are eliminated. Mutagenesis was performed on the middle one-third of pilQ, and mutants with colony morphologies consistent with the colony morphology of nonpiliated or underpiliated bacteria were selected. Nineteen mutants, each with a single amino acid substitution, were isolated and displayed diverse phenotypes in terms of PilQ multimer stability, pilus expression, transformation efficiency, and host cell adherence. The 19 mutants were grouped into five phenotypic classes based on functionality. Four of the five mutant classes fit the current model of pilus functionality, which proposes that a functional pilus assembly apparatus, not necessarily full-length pili, is required for transformation, while high levels of displayed pili are required for adherence. One class, despite having an underpiliated colony morphology, expressed high levels of pili yet adhered poorly, demonstrating that pilus expression is necessary but not sufficient for adherence and indicating that PilQ may be directly involved in host cell adherence. The collection of phenotypes expressed by these mutants suggests that PilQ has an active role in pilus expression and function.

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