scholarly journals Positively Charged Amino Acids in the Pestiviral Erns Control Cell Entry, Endoribonuclease Activity and Innate Immune Evasion

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1581
Author(s):  
Carmela Lussi ◽  
Elena de Martin ◽  
Matthias Schweizer
Keyword(s):  
Amino Acids ◽  
Binding Site ◽  
Immune Defense ◽  
Innate Immune ◽  
Cell Entry ◽  
Soluble Form ◽  
Border Disease Virus ◽  
Border Disease ◽  
Positively Charged ◽  
Endoribonuclease Activity

The genus Pestivirus, family Flaviviridae, includes four economically important viruses of livestock, i.e., bovine viral diarrhea virus-1 (BVDV-1) and -2 (BVDV-2), border disease virus (BDV) and classical swine fever virus (CSFV). Erns and Npro, both expressed uniquely by pestiviruses, counteract the host’s innate immune defense by interfering with the induction of interferon (IFN) synthesis. The structural envelope protein Erns also exists in a soluble form and, by its endoribonuclease activity, degrades immunostimulatory RNA prior to their activation of pattern recognition receptors. Here, we show that at least three out of four positively-charged residues in the C-terminal glycosaminoglycan (GAG)-binding site of BVDV-Erns are required for efficient cell entry, and that a positively charged region more upstream is not involved in cell entry but rather in RNA-binding. Moreover, the C-terminal domain on its own determines intracellular targeting, as GFP fused to the C-terminal amino acids of Erns was found at the same compartments as wt Erns. In summary, RNase activity and uptake into cells are both required for Erns to act as an IFN antagonist, and the C-terminal amphipathic helix containing the GAG-binding site determines the efficiency of cell entry and its intracellular localization.

scholarly journals Identification of specific amino acid residues in the border disease virus glycoprotein E2 that modify virus growth in pig cells but not in sheep cells

2020 ◽  
Vol 101 (11) ◽  
pp. 1170-1181
Author(s):  
Ulrik Fahnøe ◽  
Yu Deng ◽  
Nana A. Davids ◽  
Louise Lohse ◽  
Jens Bukh ◽  
...  
Keyword(s):  
Amino Acid ◽  
Disease Virus ◽  
Reverse Genetics ◽  
Serial Passage ◽  
Border Disease Virus ◽  
Virus Growth ◽  
Host Tropism ◽  
Border Disease ◽  
Glycoprotein E2 ◽  
Positively Charged

Border disease virus (BDV) envelope glycoprotein E2 is required for entry into cells and is a determinant of host tropism for sheep and pig cells. Here, we describe adaptive changes in the BDV E2 protein that modify virus replication in pig cells. To achieve this, two BDV isolates, initially collected from a pig and a sheep on the same farm, were passaged in primary sheep and pig cells in parallel with a rescued variant of the pig virus derived from a cloned full-length BDV cDNA. The pig isolate and the rescued virus shared the same amino acid sequence, but the sheep isolate differed at ten residues, including two substitutions in E2 (K771E and Y925H). During serial passage in cells, the viruses displayed clear selectivity for growth in sheep cells; only the cDNA-derived virus adapted to grow in pig cells. Sequencing revealed an amino acid substitution (Q739R) in the E2 domain DA of this rescued virus. Adaptation at the same residue (Q739K/Q739R) was also observed after passaging of the pig isolate in sheep cells. Use of reverse genetics confirmed that changing residue Q739 to R or K (each positively charged) was sufficient to achieve adaptation to pig cells. Furthermore, this change in host tropism was suppressed if Q739R was combined with K771E. Another substitution (Q728R), conferring an additional positive charge, acquired during passaging, restored the growth of the Q739R/K771E variant. Overall, this study provided evidence that specific, positively charged, residues in the E2 domain DA are crucial for pig-cell tropism of BDV.

Tuning of Electronic Properties in Conducting Polymers

2001 ◽  
Vol 66 (8) ◽  
pp. 1208-1218 ◽  
Author(s):  
Guofeng Li ◽  
Mira Josowicz ◽  
Jiří Janata
Keyword(s):  
Hydrogen Bonding ◽  
Binding Site ◽  
Binding Sites ◽  
Polymer Chains ◽  
Electronic Transitions ◽  
Weakly Bound ◽  
Ordered Structures ◽  
Doped Polymer ◽  
Positively Charged ◽  
Repeated Cycling

Structural and electronic transitions in poly(thiophenyleneiminophenylene), usually referred to as poly(phenylenesulfidephenyleneamine) (PPSA) upon electrochemical doping with LiClO4 have been investigated. The unusual electrochemical behavior of PPSA indicates that the dopant anions are bound in two energetically different sites. In the so-called "binding site", the ClO4- anion is Coulombically attracted to the positively charged S or N sites on one chain and simultaneously hydrogen-bonded with the N-H group on a neighboring polymer chain. This strong interaction causes a re-organization of the polymer chains, resulting in the formation of a networked structure linked together by these ClO4- Coulombic/hydrogen bonding "bridges". However, in the "non-binding site", the ClO4- anion is very weakly bound, involves only the electrostatic interaction and can be reversibly exchanged when the doped polymer is reduced. In the repeated cycling, the continuous and alternating influx and expulsion of ClO4- ions serves as a self-organizing process for such networked structures, giving rise to a diminishing number of available "non-binding" sites. The occurrence of these ordered structures has a major impact on the electrochemical activity and the morphology of the doped polymer. Also due to stabilization of the dopant ions, the doped polymer can be kept in a stable and desirable oxidation state, thus both work function and conductivity of the polymer can be electrochemically controlled.

scholarly journals Pestivirus infections in cervids from the Czech Republic

2009 ◽  
Vol 54 (No. 4) ◽  
pp. 191-193
Author(s):  
K. Sedlak ◽  
T. Girma ◽  
J. Holejsovsky
Keyword(s):  
Czech Republic ◽  
Cervus Elaphus ◽  
Red Deer ◽  
Competitive Inhibition ◽  
Enzyme Linked Immunosorbent Assay ◽  
Border Disease Virus ◽  
Serum Samples ◽  
The Czech Republic ◽  
Diarrhea Virus ◽  
Border Disease

372 sera of cervids from the Czech Republic were examined for antibodies to the bovine viral diarrhea virus (BVDV) and border disease virus (BDV) by competitive-inhibition enzyme-linked immunosorbent assay (ELISA), and for the presence of the BVDV by AgELISA. Antibodies to BVDV/BDV were found in 0.6% (two positive/305 tested) red deer (<I>Cervus elaphus</I>). BVDV/BDV antibodies were not found in four sika deer (<I>Cervus Nippon</I>) and 63 fallow deer (<I>Dama dama</I>). All serum samples were BVDV antigen negative. Our results confirmed that red deer in the Czech Republic are only rarely infected with Pestiviruses. This was the first survey of pestiviruses in farmed and wild cervids in the Czech Republic.

scholarly journals Primary and Memory Response of Human Monocytes to Vaccines: Role of Nanoparticulate Antigens in Inducing Innate Memory

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 931
Author(s):  
Mayra M. Ferrari Ferrari Barbosa ◽  
Alex Issamu Kanno ◽  
Leonardo Paiva Farias ◽  
Mariusz Madej ◽  
Gergö Sipos ◽  
...  
Keyword(s):  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Innate Immune ◽  
Soluble Form ◽  
Neisseria Lactamica ◽  
Particulate Form ◽  
Future Challenges ◽  
Monocytes And Macrophages

Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a subsequent challenge, aiming at better protection. In this study, using human primary monocytes in vitro, we have assessed the memory-inducing capacity of two antigenic molecules of Schistosoma mansoni in soluble form compared to the same molecules coupled to outer membrane vesicles of Neisseria lactamica. The results show that particulate challenges are much more efficient than soluble molecules in inducing innate memory, which is measured as the production of inflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10). Controls run with LPS from Klebsiella pneumoniae compared to the whole bacteria show that while LPS alone has strong memory-inducing capacity, the entire bacteria are more efficient. These data suggest that microbial antigens that are unable to induce innate immune activation can nevertheless participate in innate activation and memory when in a particulate form, which is a notion that supports the use of nanoparticulate antigens in vaccination strategies for achieving adjuvant-like effects of innate activation as well as priming for improved reactivity to future challenges.

scholarly journals Global Distribution and Genetic Heterogeneity of Border Disease Virus

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 950
Author(s):  
Cecilia Righi ◽  
Stefano Petrini ◽  
Ilaria Pierini ◽  
Monica Giammarioli ◽  
Gian Mario De Mia
Keyword(s):  
Disease Virus ◽  
Significant Risk ◽  
Small Ruminants ◽  
Control Measures ◽  
Interspecies Transmission ◽  
Economic Losses ◽  
Border Disease Virus ◽  
Diarrhea Virus ◽  
Geographical Regions ◽  
Border Disease

Border disease virus (BDV) belongs to the genus Pestivirus of the family Flaviviridae. Interspecies transmission of BDV between sheep, cattle, and pigs occurs regularly, sometimes making diagnosis a challenge. BDV can yield substantial economic losses, including prenatal and postnatal infections in lambs, which are the primary source of infection and maintenance of the virus in the population. Since BDV is antigenically and genetically related to bovine viral diarrhea virus (BVDV), it might pose a significant risk to cattle, influencing BVDV eradication campaigns. Similarly, the presence of BDV in swine herds due to pestivirus spillover between small ruminants and pigs might cause uncertainty in classical swine fever virus (CSFV) diagnostics. Therefore, knowledge of BDV epidemiology in different geographical regions will help prevent its spread and optimize control measures. Previous epidemiological studies have shown that various BDV genotypes are predominant in different countries. This review provides an overview of the spread of BDV world-wide in different host species.

The roles of grouper TANK in innate immune defense against iridovirus and nodavirus infections

2020 ◽  
Vol 104 ◽  
pp. 506-516
Author(s):  
Jingguang Wei ◽  
Chen Li ◽  
Jisheng Ou ◽  
Xin Zhang ◽  
Zetian Liu ◽  
...  
Keyword(s):  
Immune Defense ◽  
Innate Immune ◽  
Innate Immune Defense

scholarly journals Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lukas Wettstein ◽  
Tatjana Weil ◽  
Carina Conzelmann ◽  
Janis A. Müller ◽  
Rüdiger Groß ◽  
...  
Keyword(s):  
Serine Protease ◽  
Immune Defense ◽  
Innate Immune ◽  
Respiratory Pathogen ◽  
The Novel ◽  
Airway Epithelial ◽  
Protein Library ◽  
Epithelial Cultures ◽  
Alpha 1 Antitrypsin ◽  
Novel Coronavirus

AbstractSARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium. As our knowledge about innate immune factors of the respiratory tract against SARS-CoV-2 is limited, we generated and screened a peptide/protein library derived from bronchoalveolar lavage for inhibitors of SARS-CoV-2 spike-driven entry. Analysis of antiviral fractions revealed the presence of α1-antitrypsin (α1AT), a highly abundant circulating serine protease inhibitor. Here, we report that α1AT inhibits SARS-CoV-2 entry at physiological concentrations and suppresses viral replication in cell lines and primary cells including human airway epithelial cultures. We further demonstrate that α1AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion. Thus, the acute phase protein α1AT is an inhibitor of TMPRSS2 and SARS-CoV-2 entry, and may play an important role in the innate immune defense against the novel coronavirus. Our findings suggest that repurposing of α1AT-containing drugs has prospects for the therapy of COVID-19.

scholarly journals The Superagonistic Activity of Bovine Thyroid-stimulating Hormone (TSH) and the Human TR1401 TSH Analog Is Determined by Specific Amino Acids in the Hinge Region of the Human TSH Receptor

2009 ◽  
Vol 284 (24) ◽  
pp. 16317-16324 ◽  
Author(s):  
Sandra Mueller ◽  
Gunnar Kleinau ◽  
Mariusz W. Szkudlinski ◽  
Holger Jaeschke ◽  
Gerd Krause ◽  
...  
Keyword(s):  
Amino Acids ◽  
Thyroid Stimulating Hormone ◽  
Hinge Region ◽  
Camp Production ◽  
Glycoprotein Hormone ◽  
Charged Amino Acids ◽  
Bovine Thyroid ◽  
Positively Charged ◽  
Bovine Tsh ◽  
Signaling Activity

Bovine TSH (bTSH) has a higher affinity to the human TSHR (hTSHR) and a higher signaling activity than human TSH (hTSH). The molecular reasons for these phenomena are unknown. Distinct negatively charged residues (Glu297, Glu303, and Asp382) in the hinge region of the hTSHR are known to be important for bTSH binding and signaling. To investigate the potential relevance of these positions for differences between bTSH and hTSH in the interaction to the hTSHR, we determined bTSH- and hTSH-mediated cAMP production of several substitutions at these three hinge residues. To examine specific variations of hTSH, we also investigated the superagonistic hTSH analog TR1401 (TR1401), whose sequence differs from hTSH by four additional positively charged amino acids that are also present in bTSH. To characterize possible interactions between the acidic hTSHR positions Glu297, Glu303, or Asp382 and the additional basic residues of TR1401, we investigated TR1401 binding and signaling properties. Our data reveal increased cAMP signaling of the hTSHR using TR1401 and bTSH compared with hTSH. Whereas Asp382 seems to be important for bTSH- and TR1401-mediated but not for hTSH-mediated signaling, the substitution E297K exhibits a decreased signaling for all three TSH variants. Interestingly, bTSH and TR1401 showed only a slightly different binding pattern. These observations imply that specific residues of the hinge region are mediators of the superagonistic activity of bTSH and TR1401 in contrast to hTSH. Moreover, the simultaneous localization of binding components in the glycoprotein hormone molecule and the receptor hinge region permits important reevaluation of interacting hormone receptor domains.

scholarly journals Genome Sequence of Border Disease Virus Strain JSLS12-01, Isolated from Sheep in China

2013 ◽  
Vol 1 (6) ◽  
Author(s):  
X. Liu ◽  
L. Mao ◽  
W. Li ◽  
L. Yang ◽  
W. Zhang ◽  
...  
Keyword(s):  
Disease Virus ◽  
Genome Sequence ◽  
Virus Strain ◽  
Border Disease Virus ◽  
Border Disease
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