Influence of single amino acid substitutions in the hemagglutinin on the antigenic and receptor-binding properties of influenza virus B/Florida/04/2006 of Yamagata-like evolutionary lineage

Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. The type of the bond between sialic acid (SA) and the neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. Influenza A viruses of avian origin bind α2-3-sialylated glycans, while the human strains bind preferentially α2-6-sialylated ones. However, the receptor-binding specificity of influenza B viruses has not been characterized sufficiently so far. In this study, we selected the escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). The analysis of the amino acid sequences of mAb-induced escape mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution.Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. The type of the bond between sialic acid (SA) and the neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. Influenza A viruses of avian origin bind α2-3-sialylated glycans, while the human strains bind preferentially α2-6-sialylated ones. However, the receptor-binding specificity of influenza B viruses has not been characterized sufficiently so far. In this study, we selected the escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). The analysis of the amino acid sequences of mAb-induced escape mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution

Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV

A novel virus of pigs, swine hepatitis E virus (swine HEV), was recently identified and shown to be antigenically and genetically related to human HEV. In the present study, we attempted to infect specific-pathogen-free (SPF) pigs experimentally with swine HEV or with human strains of HEV. Serum samples collected from naturally infected pigs were used as the source of swine HEV. Pigs inoculated intravenously with serum samples containing swine HEV seroconverted to anti-HEV 4 to 8 weeks postinoculation, and the virus spread to an uninoculated pig. Swine HEV was detected in nasal and rectal swab materials as early as 2 weeks postinoculation and for 4 to 8 weeks thereafter. Viremia appeared 4 to 6 weeks postinoculation and lasted 1 to 3 weeks. The inoculated pigs appeared clinically normal and serum liver enzymes were not significantly elevated. In contrast, pigs were not infected when inoculated intravenously with about 105 monkey infectious doses of one of two human strains of HEV (Sar-55 or Mex-14)

Влияние единичных аминокислотных замен в гемагглютинине вируса гриппа В/Флорида/04/2006 ямагатской эволюционной линии на антигенные и рецепторсвязывающие свойства

Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. Type of the bond between sialic acid (SA) and neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. The Yamagata-like virus strains are predominantly bound to α2,6-sialylated glycans, while Victoria-like strains are bound to both α2,3- and α2,6-sialylated glycans. However, the receptor-binding specificity of influenza B viruses has not been characterized enough. In this study, we selected escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). Analysis of the amino acid sequences of mAb-induced escape-mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution.Известно, что рецептором для проникновения в клетку хозяина для вирусов гриппа A и В служат углеводные цепи, терминированные остатками нейраминовой кислоты. Тип связи между сиаловой кислотой (sialic acid, SA) и соседним остатком галактозы (Gal) является одной из главных характеристик, определяющих тип рецептора. Вирусы гриппа узнают на поверхности клетки SAα2-3Gal- или SAα2-6Gal-структуры. Птичьи изоляты вирусов гриппа A связываются с SAα2-3- сиалированными цепями, тогда как вирусы гриппа А человека – с SAα2-6Gal. Рецепторсвязывающая специфичность вирусов гриппа B изучена мало, однако известно, что вирусы разновидности Ямагата преимущественно узнают олигосахариды, терминированные SAα2-6Gal, тогда как вирусы генетической линии Виктория узнают оба типа сиалозидов. Используя четыре вируснейтрализующих моноклональных антитела (монАТ): 10F4, 8Н11, 8Н3 и 9А3, – мы получили эскейп-мутанты вируса гриппа В/Флорида/04/2006 ямагатской линии. При анализе последовательности гемагглютинина (HA) выявлено, что НА эскейп-мутантов, индуцированных монАТ 10F4, 8Н11, 8Н3 и 9А3, несут следующие единичные аминокислотные замены: 40Tyr→His, 85His→Tyr, 202Asn→Lys и 242Ser→Arg соответственно. Показано, что замены 202Asn→Lys и 242Ser→Arg приводят к изменению рецепторсвязывающей специфичности вируса. Полученные данные имеют важное значение для понимания роли отдельных аминокислотных остатков HA в формировании рецепторсвязывающих свойств вирусов гриппа В ямагатской эволюционной линии, что позволяет прогнозировать возможные пути эволюции этих вирусов

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

A cost estimation approach for IoT projects

Engineering Economics and IT management made a lot of progress towards understanding the concept of the Internet of things (IoT). Nevertheless the authors consider that some aspects of IoT project cost management still need to be further developed. At the initial stage of the research the authors were interested in the existing cost estimation approaches for IoT projects. This paper is devoted to estimation of project costs at a design stage. The general findings of the literature review revealed the problem of estimating total project cost. To establish paradigms for effective implementation and use of the Internet of things in software engineering it is necessary to consider the issues of its cost estimation. The research is focused on parametric estimate, a more accurate technique for estimating total costs and defining factors which influence the cost of IoT. The object of our inquiry are the aspects of IoT technology which influence costs. The main purpose of this paper is to help customers as they need to know the project cost before the completion. The analysis of the results allowed us to draw a conclusion that Program Evaluation and Review Technique offers the advantage of accurate estimating IoT project cost

Carvedilol therapy effects on structural and electric remodeling in chronic heart failure

Aim. To assess the effects of combination therapy with ACE inhibitors and carvedilol on cardiac remodeling, cardiac arrhythmias, and quality of life (QoL) in patients with mild to moderate chronic heart failure (CHF).Material and methods. The study included 109 patients with mild to moderate CHF, developed in arterial hypertension, coronary heart disease, or their combination with diabetes mellitus and obesity. Initial carvedilol dose was 6,25-25 mg/d. At baseline, 3, 6, and 9 months later, physical examination, biochemical assay,  lectrocardiography,QoL and clinical outcome assessment were performed. Doppler echocardiography and 24-hour electrocardiogram (ECG) monitoring were performed at baseline and 6 months later.Results. CHF therapy, including the combination of ACE inhibitor and carvedilol, was associated with reduction in structural left ventricular (LV) remodeling, as well as with systolic and diastolic LV function normalization. According to 24-hour ECG monitoring data, the total number of supraventricular (including paired and grouped) and ventricular (including paired ectopic complexes) extrasystoles significantly decreased. Combination, carvedilol-including CHF therapy resulted in significant QoL and clinical prognosis improvement.Conclusion. In patients with mild to moderate CHF, carvedilol demonstrated its clinical effectiveness, including reduced structural and electric remodeling progression

The PFAPA syndrome: current paradigm and a clinical case description

In the last decades, hereditary autoinflammatory diseases / syndromes (HAIDS) are in the focus of research and practical interests of clinicians. Common characteristics of all known HAIDS include periodic fever and systemic inflammation in combination with other clinical syndromes of certain persistence. According to current understanding, HAIDS are considered the primary immunodeficiency states, related to genetic disruption of the interplay between inflammation regulators that arise in the absence of any pathogen. Many HAIDS manifesting at childhood are associated with severe natural course and serious prognosis. An exception from this is one of the most prevalent HAIDS in children, the PFAPA syndrome, which has a favorable outcome. The term “PFAPA syndrome” is an acronym of the main clinical manifestations, such as Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis. Given the early age of its manifestation, coinciding with the time of a child's socialization, PFAPA patients can be mistakenly follow-up within the group of “frequently sick children” for many years, with high medication load. The disease is triggered by genetically determined dysregulation of congenital immunity associated with excessive production of inflammation mediators (IL-1, TNFα, IL-6, IL-12p70, etc.), with no signs of autoimmunity (autoantibodies, autoreactive T-lymphocytes). There are no specific biological markers for the PFAPA syndrome, therefore, the diagnosis is largely based on the knowledge of the main clinical symptoms of the disease, described in detail by G.S. Marshall (1987), and on the high efficacy of glucocorticosteroids. The authors present a clinical case of a 4 year and 3 month's child who suffered from repeated attacks of PFAPA-syndrome from the age of 1.5 years that recurred at a constant rate every 1.5 to 2 months. Initially, all PFAPA episodes were interpreted as manifestations of a complicated acute respiratory viral infection. Conventional therapy was ineffective. Medical examination of the parents showed chronic tonsillitis in the mother; her subsequent tonsillectomy had no effect on the course of the disease in the child. Only by the age of four, the diagnosis of the Marshall syndrome was first suspected and then confirmed. With a diagnostic and therapeutic purpose, prednisolone was administered at a dose of 1.5 mg/kg body weight with prompt normalization of the body temperature and improvement of the patients' general condition. Assessment performed at 6 months after this confirmed the adequacy of the treatment strategy, while the frequency of PFAPA episodes reduced and they became mild.Conclusion: It is necessary to increase doctors' awareness of HAIDS and of PFAPA syndrome in particular, that would ensure timely diagnosis and proper treatment