scholarly journals Linker and/or transmembrane regions of influenza A/Group-1, A/Group-2, and type B virus hemagglutinins are packed differently within trimers

2011 ◽  
Vol 1808 (7) ◽  
pp. 1843-1854 ◽  
Author(s):  
Larisa V. Kordyukova ◽  
Marina V. Serebryakova ◽  
Anton A. Polyansky ◽  
Ekaterina A. Kropotkina ◽  
Andrei V. Alexeevski ◽  
...  
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1008.2-1008
Author(s):  
L. Fang ◽  
Z. Lin ◽  
Z. Liao ◽  
O. Jin ◽  
Y. Pan ◽  
...  

Background:Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent rheumatoid arthritis (RA) and HBV infection were available by now.Objectives:To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with RA.Methods:In this 52 weeks observation, HBsAg carriers with active RA (DAS28>5.1) despite failed combined treatment with MTX and other non-biological DMARDs were enrolled. Patients must have normal liver function prior to study. All patients received therapy with tofacitinib (5mg twice daily) and concomitant MTX (10-12.5mg/w). Entecavir was prescribed preventively for patients who had a baseline HBV load >2000 copy/ml (group 1), and Lamivudin for patients with HBV load ≤ 2000 copy/ml (group 2). Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion.Results:Thirteen patients (10 female) were recruited. Nine patients had a baseline viral load >2000 copy/ml (group 1, with preventive Entecavir), and the other 4 patients had a viral load ≤ 2000 copy/ml (group 2, with preventive Lamivudin). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib.No reactivation of hepatitis B was observed in patients from group 1. One patients (female, 54 years old) from group 2 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16. An elevated viral load (4.9e6 copies/ml, baseline 1.4e3) and a HBV YMDD mutant was also found. The tofacitinib treatment continued. After prescription of Adefovir (combined with the pre-existing Lamivudin), both liver enzyme and viral load decreased to normal range in 8 weeks and remained normal throughout the study.Conclusion:An aggressive Tofacitinib + MTX therapy may be a safe option for HBsAg carriers with cs-DMARDs refractory RA. More active and effective prophylaxis strategy may be recommended to reduce the risk of HBV reactivation during the treatment.References:[1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2.Disclosure of Interests: :None declared


Science ◽  
2011 ◽  
Vol 333 (6044) ◽  
pp. 850-856 ◽  
Author(s):  
D. Corti ◽  
J. Voss ◽  
S. J. Gamblin ◽  
G. Codoni ◽  
A. Macagno ◽  
...  

PEDIATRICS ◽  
1995 ◽  
Vol 95 (4) ◽  
pp. 522-527
Author(s):  
Melanie A. Miller ◽  
Carlton K. Meschievitz ◽  
Gerard A. Ballanco ◽  
Robert S. Daum

Objective. To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic. Design. Randomized clinical trial. Setting. Suburban New Orleans pediatric population. Participants. Convenience sample of 150 healthy infants. Methods. Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197, (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide. Results. The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01). Conclusions. Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.


Immunity ◽  
2018 ◽  
Vol 48 (1) ◽  
pp. 174-184.e9 ◽  
Author(s):  
Kevin R. McCarthy ◽  
Akiko Watanabe ◽  
Masayuki Kuraoka ◽  
Khoi T. Do ◽  
Charles E. McGee ◽  
...  

Author(s):  
Bahar Öztelcan Gündüz ◽  
Erman Ataş ◽  
Bülent Ünay ◽  
Halit Halil

Abstract Objective Influenza viruses are among the most common respiratory pathogens for all age groups, and may cause seasonal outbreaks. The aim of our study was to describe the clinical characteristics of influenza cases in the 2019–2020 flu season and to study the risk factors for hospital admission and complications. Methods This was a retrospective study in 251 children (group 1: nonhospitalized; group 2: hospitalized) with influenza in the 2019–2020 flu season. Data on demographic features, influenza type, complaints, complications, and hospitalization length were collected and recorded. Results Influenza A was detected in 199 (79.3%) patients, and influenza B was detected in 52 (20.7%); 43.4% of patients were girls and 56.6% were boys. The mean age of the patients was 3.91 ± 3.3 years (16 days to 18 years). A total of 52 (20.7%) patients were hospitalized. The age of the patients in group 2 was lower than that in group 1 (3.1 vs. 4.2 years, p = 0.03). Group 2 patients were more likely to have creatine kinase (CK) elevation, febrile seizures, and physical examination abnormalities. Group 2 patients were also more likely to have influenza A. Patients with febrile seizures, chronic diseases, abnormal physical examination findings, developed complications, and additional drug use apart from oseltamivir in the treatment were also more likely to require hospitalization. Conclusion Infants and children with chronic diseases, history of febrile seizures, complications, and the use of drugs other than antiviral drugs should be carefully evaluated in case they need hospitalization. Increasing vaccination rates, initiation of antiviral treatment for selected patients, and close monitoring of patients in risk groups can decrease morbidity and mortality. Myalgias are a common complaint in patients with acute influenza infection. Previous studies suggest CK measurement be part of the work-up for the hospitalized patient with acute influenza infection.


1997 ◽  
Vol 41 (3) ◽  
pp. 530-534 ◽  
Author(s):  
S Kamimiya ◽  
B Weisblum

The erm family of 23S rRNA adenine-N6-methyltransferases confers resistance to all macrolide-lincosamide-streptograminB (MLS) antibiotics, but not all MLS antibiotics induce synthesis of Erm methyltransferase with equal efficiency in a given organism. The induction efficiency of a test panel of MLS antibiotics was studied by using two translational attenuator-lac reporter gene fusion constructs, one based on ermSV from Streptomyces viridochromogenes NRRL 2860 and the other based on ermC from Staphylococcus aureus RN2442. Four types of responses which were correlated with the macrolide ring size were seen, as follows: group 1, both ermSV and ermC were induced by the 14-membered-ring macrolides erythromycin, lankamycin, and matromycin, as well as by the lincosamide celesticetin; group 2, neither ermSV nor ermC was induced by the 12-membered-ring macrolide methymycin or by the lincosamide lincomycin or the streptogramin type B antibiotic ostreogrycin B; group 3, ermSV was selectively induced over ermC by the 16-membered-ring macrolides carbomycin, chalcomycin, cirramycin, kitasamycin, maridomycin, and tylosin; and group 4, ermC was selectively induced over ermSV by the 14-membered-ring macrolide megalomicin. These data suggest that the leader peptide determines the specificity of induction by different classes of MLS antibiotics and that for a given attenuator, a major factor which determines whether a given macrolide induces resistance is its size.


2018 ◽  
Vol 115 (16) ◽  
pp. 4240-4245 ◽  
Author(s):  
Rameshwar U. Kadam ◽  
Ian A. Wilson

The influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a foothold in the small, shallow receptor-binding site (RBS) has hindered drug design against this important target on the viral pathogen. Here, we report on the serendipitous crystallization-based discovery of a small-molecule N-cyclohexyltaurine, commonly known as the buffering agent CHES, that is able to bind to both group-1 and group-2 HAs of influenza A viruses. X-ray structural characterization of group-1 H5N1 A/Vietnam/1203/2004 (H5/Viet) and group-2 H3N2 A/Hong Kong/1/1968 (H3/HK68) HAs at 2.0-Å and 2.57-Å resolution, respectively, revealed that N-cyclohexyltaurine binds to the heart of the conserved HA RBS. N-cyclohexyltaurine mimics the binding mode of the natural receptor sialic acid and RBS-targeting bnAbs through formation of similar hydrogen bonds and CH-π interactions with the HA. In H3/HK68, N-cyclohexyltaurine also binds to a conserved pocket in the stem region, thereby exhibiting a dual-binding mode in group-2 HAs. These long-awaited structural insights into RBS recognition by a noncarbohydrate-based small molecule enhance our knowledge of how to target this important functional site and can serve as a template to guide the development of novel broad-spectrum small-molecule therapeutics against influenza virus.


2021 ◽  
Vol 19 (2) ◽  
pp. 70-75
Author(s):  
T.I. Glebova ◽  
◽  
N.G. Klivleyeva ◽  
A.M. Baimukhametova ◽  
N.T. Saktaganov ◽  
...  

Objective. Detection of influenza viruses among the population on the territory of the Northern and Western Kazakhstan during the 2018–2019 epidemic season. Patients and methods. The study involved 835 patients with ARVI symptoms. Biological samples were screened in real-time polymerase chain reaction (RT-PCR), hemagglutination inhibition (HAI) assay, and enzyme-linked immunosorbent assay (ELISA). Hemagglutinating agents were isolated in 9-10-day-old developing chicken embryos. Identification of isolates was carried out in RT-PCR and HAI assay. Results. 936 clinical samples (835 nasopharyngeal swabs and 101 blood serums) were collected from patients in the Northern (North Kazakhstan and Pavlodar oblasts) and Western (West Kazakhstan oblast) regions during the 2018–2019 epidemic season. Primary screening of 835 nasopharyngeal swabs revealed the genetic material of influenza virus in 20.48%, influenza A virus in 20.36%, and influenza B virus in 0.12%. Subtyping of PCR positive samples for influenza type A virus showed the presence of the genetic material of influenza A/H1N1pdm09 virus in 14.01%, A/H3N2 virus in 4.91%. The virus subtype was not established in 1.66%. Virological examination of nasopharyngeal swabs led to obtaining 14 isolates, of which 13 were identified as influenza A/H1N1pdm09 viruses and 1 as influenza A/H3N2 virus. Serological studies of 101 blood serums in the HAI assay showed the presence of antihemagglutinins against influenza A/H1N1pdm09 virus in 28.71%, A/H3N2 virus in 30.69%, type B virus in 3.96% of the total number of samples. Antibodies simultaneously against two subtypes of influenza viruses (A and B) were detected in 12.87% of cases. In ELISA antibodies against influenza A/H1N1 virus were revealed in 24.75% of cases, A/H3N2 virus in 19.80%, type B virus in 14.85%. Antibodies simultaneously against two types of influenza viruses (A and B) were detected in 2.97% of blood serums. Conclusion. The results of virological and serological studies presented in the paper suggest circulation of influenza A/H1N1pdm09, A/H3N2, and type B viruses in the examined oblasts of Kazakhstan during the 2018–2019 season. Key words: virus, hemagglutinin, influenza, diagnosis, isolate, neuraminidase, circulation


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