scholarly journals Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza

2020 ◽  
Author(s):  
Ayako Ohno ◽  
Nobuo Maita ◽  
Takanori Tabata ◽  
Hikaru Nagano ◽  
Kyohei Arita ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Homology Model ◽  
Side Chain ◽  
Pathogenic Avian Influenza ◽  
Host Cell Proteins ◽  
Extracellular Region ◽  
Surface Envelope ◽  
Α Helix ◽  
High Pathogenic ◽  
High Pathogenic Avian Influenza

AbstractViral infection is triggered when a surface envelope glycoprotein, hemagglutinin (HA), is cleaved by host cell proteins of the transmembrane protease serine (TMPRSS) family. The extracellular region of TMPRSS-2, -3, -4, and MSPL are composed of LDLA, SRCR, and SPD domains. MSPL can cleave the consensus multibasic (R-X-X/R-R) and monobasic (Q(E)-T/X-R) motifs on HA, while TMPRSS2 or -4 only cleaves monobasic motifs. To better understand HA cleavage mediated by MSPL, we solved the crystal structure of the extracellular region of human MSPL in complex with the furin inhibitor. The structure revealed that three domains are gathered around the C-terminal α-helix of the SPD domain. The furin inhibitor structure shows that the side chain of P1-Arg inserts into the highly conserved S1 pocket, whereas the side chain of P2-Lys interacts with the Asp/Glu-rich 99 loop that is unique to MSPL. We also constructed a homology model of TMPRSS2, which is identified as an initiator of SARS-CoV-2 infection. The model suggests that TMPRSS2 is more suitable for Ala/Val residues at the P2 site than Lys/Arg residues.

scholarly journals Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza

2021 ◽  
Vol 4 (6) ◽  
pp. e202000849
Author(s):  
Ayako Ohno ◽  
Nobuo Maita ◽  
Takanori Tabata ◽  
Hikaru Nagano ◽  
Kyohei Arita ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Avian Influenza ◽  
Serine Proteases ◽  
Homology Model ◽  
Influenza Viruses ◽  
Substrate Analog ◽  
Extracellular Region ◽  
Α Helix ◽  
High Pathogenic ◽  
High Pathogenic Avian Influenza

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.

scholarly journals Dynamics of low and high pathogenic avian influenza in wild and domestic bird populations

2015 ◽  
Vol 10 (1) ◽  
pp. 104-139 ◽  
Author(s):  
Necibe Tuncer ◽  
Juan Torres ◽  
Maia Martcheva ◽  
Michael Barfield ◽  
Robert D. Holt
Keyword(s):  
Avian Influenza ◽  
Bird Populations ◽  
Pathogenic Avian Influenza ◽  
Domestic Bird ◽  
High Pathogenic ◽  
High Pathogenic Avian Influenza

Modelling high pathogenic avian influenza outbreaks in the commercial poultry industry

2019 ◽  
Vol 126 ◽  
pp. 59-71 ◽  
Author(s):  
Belinda Barnes ◽  
Angela Scott ◽  
Marta Hernandez-Jover ◽  
Jenny-Ann Toribio ◽  
Barbara Moloney ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Poultry Industry ◽  
Pathogenic Avian Influenza ◽  
Commercial Poultry ◽  
Influenza Outbreaks ◽  
High Pathogenic ◽  
High Pathogenic Avian Influenza

scholarly journals Strategies to control high pathogenic avian influenza (HPAI) in the Belgian poultry sector

2009 ◽  
Vol 25 (5-6-1) ◽  
pp. 373-385 ◽  
Author(s):  
Y. Vandendriessche ◽  
X. Gellynck ◽  
H. Saatkamp ◽  
J. Viaene
Keyword(s):  
Avian Influenza ◽  
Control Strategies ◽  
Control Measures ◽  
Economic Losses ◽  
Economic Damage ◽  
Correct Identification ◽  
Economic Point ◽  
Pathogenic Avian Influenza ◽  
High Pathogenic ◽  
High Pathogenic Avian Influenza

High Pathogenic Avian Influenza (HPAI) may pose a major threat for the Belgium poultry sector, as an outbreak of HPAI results in tremendous economic losses. In order to reduce the economic damage for an outbreak, different strategies to control HPAI are evaluated. In a first stage the structure of the Belgium poultry sector is described and risks are analyzed. The actual risks are dependent of the intensive character of poultry farming in Belgium, the large number of transport movements of living poultry, the presence of sensitive nature areas and the border with the Netherlands where the poultry density is even larger. In a second stage the possible intervention strategies are evaluated. Starting from the current regulation, two strategies are worked out: stamping out and emergency vaccination. The success of emergency vaccination is associated with the correct identification of compartments at risk, prompt deployment of emergency vaccines, rapid enforcement of appropriate complementary control measures and also the level of being ready. In a third stage an economic analysis of control strategies for HPAI outbreaks is made. Results suggest that from an economic point of view, stamping-out is at farm level a better option then emergency vaccination within the current context.

scholarly journals Ammonia Disinfection of Hatchery Waste for Elimination of Single-Stranded RNA Viruses

2011 ◽  
Vol 77 (12) ◽  
pp. 3960-3966 ◽  
Author(s):  
Eva Emmoth ◽  
Jakob Ottoson ◽  
Ann Albihn ◽  
Sándor Belák ◽  
Björn Vinnerås
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Rna Viruses ◽  
Hepatitis E ◽  
Inactivation Kinetics ◽  
Pathogenic Avian Influenza ◽  
Pathogenic Avian Influenza Virus ◽  
High Pathogenic ◽  
High Pathogenic Avian Influenza

ABSTRACTHatchery waste, an animal by-product of the poultry industry, needs sanitation treatment before further use as fertilizer or as a substrate in biogas or composting plants, owing to the potential presence of opportunistic pathogens, including zoonotic viruses. Effective sanitation is also important in viral epizootic outbreaks and as a routine, ensuring high hygiene standards on farms. This study examined the use of ammonia at different concentrations and temperatures to disinfect hatchery waste. Inactivation kinetics of high-pathogenic avian influenza virus H7N1 and low-pathogenic avian influenza virus H5N3, as representatives of notifiable avian viral diseases, were determined in spiked hatchery waste. Bovine parainfluenza virus type 3, feline coronavirus, and feline calicivirus were used as models for other important avian pathogens, such as Newcastle disease virus, infectious bronchitis virus, and avian hepatitis E virus. Bacteriophage MS2 was also monitored as a stable indicator. Coronavirus was the most sensitive virus, with decimal reduction (D) values of 1.2 and 0.63 h after addition of 0.5% (wt/wt) ammonia at 14 and 25°C, respectively. Under similar conditions, high-pathogenic avian influenza H7N1 was the most resistant, withDvalues of 3.0 and 1.4 h. MS2 was more resistant than the viruses to all treatments and proved to be a suitable indicator of viral inactivation. The results indicate that ammonia treatment of hatchery waste is efficient in inactivating enveloped and naked single-stranded RNA viruses. Based on theDvalues and confidence intervals obtained, guidelines for treatment were proposed, and one was successfully validated at full scale at a hatchery, with MS2 added to hatchery waste.

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