Sphingolipids in viral infection

2015 ◽  
Vol 396 (6-7) ◽  
pp. 585-595 ◽  
Author(s):  
Jürgen Schneider-Schaulies ◽  
Sibylle Schneider-Schaulies
Keyword(s):  
Measles Virus ◽  
Influenza A ◽  
Sindbis Virus ◽  
Intracellular Transport ◽  
Ebola Virus ◽  
Surface Expression ◽  
Sphingolipid Metabolism ◽  
C Protein ◽  
Protein Receptors ◽  
Niemann Pick

Abstract Viruses exploit membranes and their components such as sphingolipids in all steps of their life cycle including attachment and membrane fusion, intracellular transport, replication, protein sorting and budding. Examples for sphingolipid-dependent virus entry are found for: human immunodeficiency virus (HIV), which besides its protein receptors also interacts with glycosphingolipids (GSLs); rhinovirus, which promotes the formation of ceramide-enriched platforms and endocytosis; or measles virus (MV), which induces the surface expression of its own receptor CD150 via activation of sphingomyelinases (SMases). While SMase activation was implicated in Ebola virus (EBOV) attachment, the virus utilizes the cholesterol transporter Niemann-Pick C protein 1 (NPC1) as ‘intracellular’ entry receptor after uptake into endosomes. Differential activities of SMases also affect the intracellular milieu required for virus replication. Sindbis virus (SINV), for example, replicates better in cells lacking acid SMase (ASMase). Defined lipid compositions of viral assembly and budding sites influence virus release and infectivity, as found for hepatitis C virus (HCV) or HIV. And finally, viruses manipulate cellular signaling and the sphingolipid metabolism to their advantage, as for example influenza A virus (IAV), which activates sphingosine kinase 1 and the transcription factor NF-κB.

scholarly journals The Manifold Roles of Sphingolipids in Viral Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Elita Avota ◽  
Jochen Bodem ◽  
Janice Chithelen ◽  
Putri Mandasari ◽  
Niklas Beyersdorf ◽  
...  
Keyword(s):  
Measles Virus ◽  
Influenza A ◽  
Ebola Virus ◽  
Viral Infections ◽  
Virus Assembly ◽  
Sphingolipid Metabolism ◽  
Targeted Interventions ◽  
Antiviral Therapies ◽  
Essential Components ◽  
Endosomal Membranes

Sphingolipids are essential components of eukaryotic cells. In this review, we want to exemplarily illustrate what is known about the interactions of sphingolipids with various viruses at different steps of their replication cycles. This includes structural interactions during entry at the plasma membrane or endosomal membranes, early interactions leading to sphingolipid-mediated signal transduction, interactions with internal membranes and lipids during replication, and interactions during virus assembly and budding. Targeted interventions in sphingolipid metabolism – as far as they can be tolerated by cells and organisms – may open novel possibilities to support antiviral therapies. Human immunodeficiency virus type 1 (HIV-1) infections have intensively been studied, but for other viral infections, such as influenza A virus (IAV), measles virus (MV), hepatitis C virus (HCV), dengue virus, Ebola virus, and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), investigations are still in their beginnings. As many inhibitors of sphingolipid metabolism are already in clinical use against other diseases, repurposing studies for applications in some viral infections appear to be a promising approach.

scholarly journals Reduced Nucleoprotein availability impairs negative-sense RNA virus replication and promotes host recognition

2021 ◽  
Author(s):  
Benjamin E. Nilsson-Payant ◽  
Daniel Blanco-Melo ◽  
Skyler Uhl ◽  
Beatriz Escudero-Pérez ◽  
Silke Olschewski ◽  
...  
Keyword(s):  
Host Response ◽  
Measles Virus ◽  
Influenza A ◽  
Ebola Virus ◽  
Rna Viruses ◽  
Viral Rna ◽  
Genome Replication ◽  
Replication Machinery ◽  
Molecular Patterns ◽  
Negative Sense

Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent RNA polymerases (RdRp) to replicate and transcribe their viral genomes. Their replication machinery consists of an RdRp bound to viral RNA which is wound around a nucleoprotein (NP) scaffold, forming a viral ribonucleoprotein complex. NSV NP is known to regulate transcription and replication of genomic RNA, however its role in maintaining and protecting the viral genetic material is unknown. Here, we exploited host microRNA expression to target NP of influenza A virus and Sendai virus to ascertain how this would impact genomic levels and the host response to infection. We find that in addition to inducing a drastic decrease in genome replication, the antiviral host response in the absence of NP is dramatically enhanced. Additionally, our data shows that insufficient levels of NP prevent the replication machinery of these NSVs to process full-length genomes, resulting in aberrant replication products which form pathogen-associated molecular patterns in the process. These dynamics facilitate immune recognition by cellular pattern recognition receptors leading to a strong host antiviral response. Moreover, we observe that the consequences of limiting NP levels are universal amongst NSVs including Ebola virus, Lassa virus and Measles virus. Overall, these results provide new insights into viral genome replication of negative-sense RNA viruses and highlight novel avenues towards developing effective antiviral strategies, adjuvants, and/or live-attenuated vaccines. IMPORTANCE Negative-sense RNA viruses comprise some of the most important known human pathogens, including influenza A virus, measles virus and Ebola virus. These viruses possess RNA genomes that are unreadable to the host as they require specific viral RNA dependent RNA polymerases in conjunction with other viral proteins such as nucleoprotein to be replicated and transcribed. As this process generates a significant amount of pathogen-associated molecular patterns, this phylum of viruses can result in a robust induction of the intrinsic host cellular response. To circumvent these defenses, these viruses form tightly regulated ribonucleoprotein replication complexes in order to protect their genomes from detection and to prevent excessive aberrant replication. Here we demonstrate the balance that negative-sense RNA viruses must achieve to both replicate efficiently and to avoid induction of the host defenses.

scholarly journals EXPRESS: Retrospective study of clinical characteristics and viral etiologies of patients with viral pneumonia in Beijing

2021 ◽  
pp. 204589402110110
Author(s):  
Xiang Zhao ◽  
Yao Meng ◽  
Duo Li ◽  
Zhaomin Feng ◽  
Weijuan Huang ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Influenza A ◽  
Clinical Characteristics ◽  
Ebola Virus ◽  
Treatment Strategies ◽  
Lavage Fluid ◽  
Viral Pneumonia ◽  
Chip Technology ◽  
Viral Influenza ◽  
Simplex Virus

Aims: The virus is common in patients with viral pneumonia. However, the viral etiology and clinical features of patients with viral pneumonia in China remain unclear. The main purpose of this study was to analyze the viral causes and epidemiology of patients with viral pneumonia in Beijing, which can significantly improve the pertinence and accuracy of clinical treatment of the disease. Methods: Firstly, 1,539 respiratory specimens of pneumonia (oropharyngeal swabs, nasopharyngeal swabs, saliva samples and bronchoalveolar lavage fluid) were collected from 19 hospitals in Beijing from September 2015 to August 2018. Then, TaqMan low-density microfluidic chip technology was used to detect viral pneumonia specimens in 1,539 respiratory tract specimens of pneumonia, and determine the types of viral bacteria in them. Lastly, the analysis of demographic, clinical and etiological data of patients with viral pneumonia was performed. Results: The results showed that among the 1,539 respiratory tract specimens with pneumonia, 760 were detected as viral pneumonia specimens, with a positive rate of 49.4%. Among which, 467 were infected with mono-viral and 293 were infected with multi-viral. Influenza A virus (Flu A), mycoplasma pneumoniae (MPn), ebola virus (EBV) and herpes simplex virus type 1 (HSV-1) were the major viral components in the samples of these patients. Furthermore, these viral species were significantly associated with sample sources, onset season and certain clinical characteristics. Discussion: Our findings may provide corresponding treatment strategies for viral pneumonia patients infected with specific viruses.

scholarly journals Capturing Enveloped Viruses on Affinity Grids for Downstream Cryo-Electron Microscopy Applications

2013 ◽  
Vol 20 (1) ◽  
pp. 164-174 ◽  
Author(s):  
Gabriella Kiss ◽  
Xuemin Chen ◽  
Melinda A. Brindley ◽  
Patricia Campbell ◽  
Claudio L. Afonso ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Measles Virus ◽  
Influenza A ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Nitrilotriacetic Acid ◽  
Dimensional Structure ◽  
Enveloped Viruses ◽  
Cryo Electron Microscopy ◽  
Human Immunodeficiency Virus Virus

AbstractElectron microscopy (EM), cryo-electron microscopy (cryo-EM), and cryo-electron tomography (cryo-ET) are essential techniques used for characterizing basic virus morphology and determining the three-dimensional structure of viruses. Enveloped viruses, which contain an outer lipoprotein coat, constitute the largest group of pathogenic viruses to humans. The purification of enveloped viruses from cell culture presents certain challenges. Specifically, the inclusion of host-membrane-derived vesicles, the complete destruction of the viruses, and the disruption of the internal architecture of individual virus particles. Here, we present a strategy for capturing enveloped viruses on affinity grids (AG) for use in both conventional EM and cryo-EM/ET applications. We examined the utility of AG for the selective capture of human immunodeficiency virus virus-like particles, influenza A, and measles virus. We applied nickel-nitrilotriacetic acid lipid layers in combination with molecular adaptors to selectively adhere the viruses to the AG surface. This further development of the AG method may prove essential for the gentle and selective purification of enveloped viruses directly onto EM grids for ultrastructural analyses.

scholarly journals Cell tropism of wild-type measles virus is affected by amino acid substitutions in the P, V and M proteins, or by a truncation in the C protein

2004 ◽  
Vol 85 (10) ◽  
pp. 3001-3006 ◽  
Author(s):  
Naoko Miyajima ◽  
Makoto Takeda ◽  
Masato Tashiro ◽  
Koji Hashimoto ◽  
Yusuke Yanagi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Measles Virus ◽  
M Protein ◽  
Amino Acid Difference ◽  
Cell Tropism ◽  
Wild Type ◽  
M Gene ◽  
Nucleotide Difference ◽  
Virus Growth ◽  
C Protein

Two nucleotide differences in the P/C/V and M genes between B95a cell- and Vero cell-isolated wild-type measles viruses (MV) have previously been found from the same patient. The nucleotide difference in the P/C/V gene resulted in an amino acid difference (M175I) in the P and V proteins and a 19 aa deletion in the C protein. The nucleotide difference in the M gene resulted in an amino acid difference (P64H) in the M protein. To verify this result and to examine further whether the amino acid difference or truncation is important for MV cell tropism, recombinant MV strains containing one of the two nucleotide substitutions, or both, were generated. It was found that the P64H substitution in the M protein was important for efficient virus growth and dissemination in Vero cells and that the M175I substitution in the P and V protein or truncation of the C protein was required for optimal growth.

Surface expression of influenza virus neuraminidase, an amino-terminally anchored viral membrane glycoprotein, in polarized epithelial cells

1985 ◽  
Vol 5 (9) ◽  
pp. 2181-2189
Author(s):  
L V Jones ◽  
R W Compans ◽  
A R Davis ◽  
T J Bos ◽  
D P Nayak
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Surface Expression ◽  
African Green Monkey ◽  
Monkey Kidney ◽  
Kidney Cells ◽  
African Green Monkey Kidney ◽  
Amino Terminal ◽  
Green Monkey ◽  
Na Gene

We have investigated the site of surface expression of the neuraminidase (NA) glycoprotein of influenza A virus, which, in contrast to the hemagglutinin, is bound to membranes by hydrophobic residues near the NH2-terminus. Madin-Darby canine kidney or primary African green monkey kidney cells infected with influenza A/WSN/33 virus and subsequently labeled with monoclonal antibody to the NA and then with a colloidal gold- or ferritin-conjugated second antibody exhibited specific labeling of apical surfaces. Using simian virus 40 late expression vectors, we also studied the surface expression of the complete NA gene (SNC) and a truncated NA gene (SN10) in either primary or a polarized continuous line (MA104) of African green monkey kidney cells. The polypeptides encoded by the cloned NA cDNAs were expressed on the surface of both cell types. Analysis of [3H]mannose-labeled polypeptides from recombinant virus-infected MA104 cells showed that the products of cloned NA cDNA comigrated with glycosylated NA from influenza virus-infected cells. Both the complete and the truncated glycoproteins were found to be preferentially expressed on apical plasma membranes, as detected by immunogold labeling. These results indicate that the NA polypeptide contains structural features capable of directing the transport of the protein to apical cell surfaces and the first 10 amino-terminal residues of the NA polypeptide are not involved in this process.

The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity

2019 ◽  
Vol 400 (5) ◽  
pp. 629-638 ◽  
Author(s):  
Darja Kanduc
Keyword(s):  
Measles Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Sequence Similarity ◽  
Eukaryotic Cell ◽  
Point Of View ◽  
Peptide Sequence ◽  
Human Viruses ◽  
Archaeal Ancestor ◽  
Borna Disease

Abstract Analyses of the peptide sharing between five common human viruses (Borna disease virus, influenza A virus, measles virus, mumps virus and rubella virus) and the human proteome highlight a massive viral vs. human peptide overlap that is mathematically unexpected. Evolutionarily, the data underscore a strict relationship between viruses and the origin of eukaryotic cells. Indeed, according to the viral eukaryogenesis hypothesis and in light of the endosymbiotic theory, the first eukaryotic cell (our lineage) originated as a consortium consisting of an archaeal ancestor of the eukaryotic cytoplasm, a bacterial ancestor of the mitochondria and a viral ancestor of the nucleus. From a pathologic point of view, the peptide sequence similarity between viruses and humans may provide a molecular platform for autoimmune crossreactions during immune responses following viral infections/immunizations.

scholarly journals Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity

2017 ◽  
Vol 114 (38) ◽  
pp. E7987-E7996 ◽  
Author(s):  
Jinwoo Lee ◽  
David A. Nyenhuis ◽  
Elizabeth A. Nelson ◽  
David S. Cafiso ◽  
Judith M. White ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Viral Entry ◽  
Ebola Virus ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Virus Envelope ◽  
Tm Domain ◽  
Virus Envelope Protein ◽  
Niemann Pick ◽  
Fusion Loop

Ebolavirus (EBOV), an enveloped filamentous RNA virus causing severe hemorrhagic fever, enters cells by macropinocytosis and membrane fusion in a late endosomal compartment. Fusion is mediated by the EBOV envelope glycoprotein GP, which consists of subunits GP1 and GP2. GP1 binds to cellular receptors, including Niemann-Pick C1 (NPC1) protein, and GP2 is responsible for low pH-induced membrane fusion. Proteolytic cleavage and NPC1 binding at endosomal pH lead to conformational rearrangements of GP2 that include exposing the hydrophobic fusion loop (FL) for insertion into the cellular target membrane and forming a six-helix bundle structure. Although major portions of the GP2 structure have been solved in pre- and postfusion states and although current models place the transmembrane (TM) and FL domains of GP2 in close proximity at critical steps of membrane fusion, their structures in membrane environments, and especially interactions between them, have not yet been characterized. Here, we present the structure of the membrane proximal external region (MPER) connected to the TM domain: i.e., the missing parts of the EBOV GP2 structure. The structure, solved by solution NMR and EPR spectroscopy in membrane-mimetic environments, consists of a helix-turn-helix architecture that is independent of pH. Moreover, the MPER region is shown to interact in the membrane interface with the previously determined structure of the EBOV FL through several critical aromatic residues. Mutation of aromatic and neighboring residues in both binding partners decreases fusion and viral entry, highlighting the functional importance of the MPER/TM–FL interaction in EBOV entry and fusion.

scholarly journals Elongation of the Cytoplasmic Tail Interferes with the Fusion Activity of Influenza Virus Hemagglutinin

1998 ◽  
Vol 72 (5) ◽  
pp. 3554-3559 ◽  
Author(s):  
Masanobu Ohuchi ◽  
Christian Fischer ◽  
Reiko Ohuchi ◽  
Astrid Herwig ◽  
Hans-Dieter Klenk
Keyword(s):  
Intracellular Transport ◽  
Critical Role ◽  
Simian Virus 40 ◽  
Cytoplasmic Tail ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Simian Virus ◽  
Cell Surface Expression ◽  
Erythrocyte Membranes ◽  
Fusion Pores

ABSTRACT The hemagglutinin (HA) of fowl plague virus was lengthened and shortened by site-specific mutagenesis at the cytoplasmic tail, and the effects of these modifications on HA functions were analyzed after expression from a simian virus 40 vector. Elongation of the tail by the addition of one to six histidine (His) residues did not interfere with intracellular transport, glycosylation, proteolytic cleavage, acylation, cell surface expression, and hemadsorption. However, the ability to induce syncytia at a low pH decreased dramatically depending on the number of His residues added. Partial fusion (hemifusion), assayed by fluorescence transfer from octadecylrhodamine-labeled erythrocyte membranes, was also reduced, but even with the mutant carrying six His residues, significant transfer was observed. However, when the formation of fusion pores was examined with hydrophilic fluorescent calcein, transfer from erythrocytes to HA-expressing cells was not observed with the mutant carrying six histidine residues. The addition of different amino acids to the cytoplasmic tail of HA caused an inhibitory effect similar to that caused by the addition of His. On the other hand, a mutant lacking the cytoplasmic tail was still able to fuse at a reduced level. These results demonstrate that elongation of the cytoplasmic tail interferes with the formation and enlargement of fusion pores. Thus, the length of the cytoplasmic tail plays a critical role in the fusion process.

Sign in / Sign up

Export Citation Format

Share Document