Influenza virus infection and postviral bacterial pneumonia pathogenesis induced by different subtypes of influenza virus in mice

Secondary bacterial infections after influenza virus infection further increase morbidity and mortality due to influenza. Despite of seasonal influenza vaccination, antiviral drugs and antibiotics are widely used in viral/bacterial pneumonia therapy. Therefore, further comprehensive study of the infection pathogenesis is relevant. Murine models for influenza virus infection were reproduced with different virus subtypes A/California/04/2009MA (pandemic H1N1 2009), A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/69 (H3N2), Anadyr/177/2009 (H1N1) and for post-influenza bacterial pneumonia caused by the Gram-positive Staphylococcus aureus. After the infection occurs, its pathogenic features were detected by daily monitoring the mortality (survival) and morbidity rate (body weight loss) and, in addition, viral pathogenesis also was evaluated by assessing virus replication (viral titer) and humoral immune responses (production of pro- and anti-inflammatory cytokines) in respiratory tract of infected mice including during antiviral (oseltamivir) and antibacterial (cefuroxime) therapy. Mortality and virus titer in the infected mice did not differ significantly between the groups of different influenza A virus subtypes. However, production of cytokines (IL-10, IFNg, TNFa) and weight gain proved to be different. Mortality of the mice reached 100% after secondary bacterial infection, whereas IFNg and TNFa levels in mice lung increased reached maximal values in the treated groups. Viral subtype A/California/04/2009MA of influenza A was most pathogenic in mouse model of secondary bacterial pneumonia. Antiviral and antibacterial treatment caused a decrease in mortality, reduced viral titers in lungs, and retain body weight gain of mice. According to these points, the treatment groups did not significantly differ from each other. At the same time, it should be noted that the cytokine production significantly decreased in the treated groups, and IL-10 and IFNg levels in lungs were different, that may be due to therapeutic mechanisms of these drugs. Thus, antiviral therapy for influenza infection and combination therapy for viralbacterial pneumonia can be an effective tool to reduce mortality of influenza

EFFECT AUTOMOBILE WHEEL RIM ROLLING DISK OF SILICONE ON ITS STRUCTURE AND MECHANICAL PROPERTIES

Исследованы микроструктура и механические свойства литых дисков автомобильных колес из силумина марки АК7 после раскатки обода. В результате деформации и последующей термической обработки достигнуто повышение механических свойств.The microstructure and mechanical properties of cast wheel discs from silumin brand AK7 after rolling the rim. As a result, deformation and subsequent heat treatment achieved improvement in the mechanical properties

Peculiarities of the influenza viruses circulation and their properties during 2018-2019 epidemic season in Russia and countries of the Northern Hemisphere

Objective. To identify the drift variability of influenza viruses during the period of epidemic rise in the incidence of acute respiratory viral infections in the period 2018-2019. The biological and molecular-genetic properties of epidemic strains isolated in certain territories of the Russian Federation were studied and compared with data from the countries of the Northern Hemisphere. Materials and methods. A range of laboratory diagnostic methods has been applied, including immune fluorescence, RT-PCR, sequencing, methods for determining sensitivity to influenza drugs and receptor specificity. Results and discussion. The proportion of influenza viruses was as follows: A (H1N1) pdm09 - 53 %, A (H3N2) - 46 %, B - about 1 %. Cases of severe acute respiratory infections have most often been associated with influenza A(H1N1) pdm09 virus. According to antigenic properties, isolated strains corresponded to the properties of vaccine viruses (A/Michigan/45/2015 - by 99.6 % and A/Singapore INFIMH-16-0019/2016 - by 86 %). The heterogeneity of influenza A virus strains population was revealed as regards individual mutations in hemaglutinin. The influenza B virus population was equally represented by both evolutionary lines (B/Victoria and B/Yamagata-like). Receptor specificity was favorable for the course and outcome of the disease. Among 70 studied epidemic strains, no strains resistant to anti-neuraminidase drugs, oseltamivir and zanamivir, were detected. The article presents WHO recommendations on the composition of influenza vaccines for the countries of the Northern Hemisphere for 2019-2020, provides data on cases of human infection with avian influenza viruses A(H5N1), A(H5N6), A(H7N9) and A(H9N2)

Заболеваемость гриппом в январе-марте 2016 г. в Российской Федерации: эпидемический и пандемический потенциал вируса гриппа A(H1N1)pdm09

The World Health Organization (WHO) searches influenza virus circulation in community and in natural biocenosis, studies virus strains and their properties, develops diagnostic methods and preventive measures since 1940th worldwide because of epidemic actuality and high pandemic potential of the influenza virus. The Federal Influenza Center (including Federal Research Institute of Influenza, Saint-Petersburg, and the Center of Virus Ecology, D.I.Ivanovskiy Virology Institute, Honorary Academician N.F.GamaleyaFederal Research Center of Epidemiology and Microbiology, Federal Research Center for Epidemiology and Microbiology, Moscow) performs similar work in Russia in close cooperation with WHO within the framework of the International Programme of Influenza Monitoring. A(H1N1)pdm09 influenza virus dominated in the Northern Hemisphere in the 2015 – 2016 epidemic season. Morbidity growth was noted from the end of January, 2016, to the beginning of March, 2016. The peak morbidity at the 5th week of the year exceeded the epidemic threshold (132 cases per 10,000 of population) and morbidity in the 2014 – 2015 season significantly and approached to the peak morbidity of the 2009 – 2010 epidemic season. The epidemic growth in Russian Federation was provided by three influenza viruses: A(H1N1)pdm09, В and A (H3N2). A(H1N1)pdm09 virus caused 18% of all acute respiratory diseases and accounted for 84% of circulating influenza viruses.Flu was diagnosed in patients of different age with maximal frequency in 3- to 6-year old children. Peak admission number was registered at 5 and 6 weeks (3,538 and 4,109 cases, respectively); this number exceeded the similar parameter of the 2009 – 2010 season. Patients of 15 to 64 years old were admitted more often including those with acute respiratory infection. Two hundred and thirty nine deaths were registered to the 5th of April, 2016, according to data from the Federal Influenza Center and the Center of Virus Ecology. The diagnosis of A(H1N1)pdm09 flu was confirmed in 97.9% of deaths. Molecular analysis of isolated strains of A(H1N1)pdm09 influenza virus revealed amino acid substitutions in receptor binding site and SA site of hemagglutinin and in genes coding intrinsic proteins PA, NP, M1, and NS1. Influenza virus strains resistive to anti-neuraminidase drugs were encountered in #< 1% in the Northern Hemisphere countries. No strains studied were sensitive to adamantine derivates.Актуальность. С 1947 г. в связи с эпидемической актуальностью и высоким пандемическим потенциалом вируса гриппа типа А по инициативе Всемирной организации здравоохранения (ВОЗ) организована Глобальная система по надзору за гриппом и ответу (Global Influenza Surveillance and Response System – GISRS), которая в настоящее время представлена 6 сотрудничающими центрами по гриппу, 143 национальными центрами по гриппу в 113 странах, а также производителями гриппозных вакцин. Российская Федерация представлена в этой системе двумя национальными центрами – Федеральным центром по гриппу (ФЦГ) ФГБУ «Научно-исследовательский институт гриппа» Минздрава России (Санкт-Петербург) и Центром экологии и эпидемиологии гриппа (ЦЭЭГ) Института вирусологии им. Д.И.Ивановского ФГБУ «Федеральный научно-исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф.Гамалеи» Минздрава России (Москва). Оба центра осуществляют еженедельный надзор за циркуляцией вирусов гриппа в 59 городах Российской Федерации, который предполагает анализ заболеваемости, госпитализации, летальных случаев от гриппа и острой респираторной вирусной инфекции (ОРВИ) в разных возрастных группах, а также проведение диагностики с помощью широкого спектра лабораторных методов. Материалы и методы. В странах Северного полушария в эпидемическом сезоне 2015–2016 гг. в этиологии подъема заболеваемости доминировал вирус гриппа A(H1N1)pdm09. Подъем заболеваемости гриппом в России зарегистрирован с конца января до начала марта 2016 г. Показатель заболеваемости на пике эпидемии (5-я неделя 2016 г.), значительно превысив эпидемический порог (132 случая на 10 тыс. населения) и значение сезона 2014–2015 гг., отмечен на уровне эпидемического сезона 2009–2010 гг. Результаты. Этиологическую структуру эпидемического подъема заболеваемости в РФ определили 3 вируса гриппа – A(H1N1)pdm09, В и A(H3N2) при разном долевом участии. Грипп A(H1N1)pdm09 в структуре ОРВИ составила 18,0 %, в структуре циркулирующих вирусов гриппа – 84,0 %. Заболеваемость зарегистрирована во всех возрастных группах. Бόльшая вовлеченность в эпидемический процесс зафиксирована у детей 3–6 лет. Максимальное число госпитализаций отмечено на 5-й и 6-й неделях 2016 г. – 3 538 и 4 109 случаев соответственно, что превысило показатели сезона 2009–2010 гг. Наибольшее число случаев госпитализации, в т. ч. с тяжелой острой респираторной инфекцией, отмечено в возрастной группе 15–64 лет. По данным ФЦГ и ЦЭЭГ, на 05.04.16 зарегистрировано 239 летальных исходов. В 97,9 % случаев лабораторными исследованиями подтвержден грипп A(H1N1)pdm09. Заключение. По результатам молекулярно-генетического анализа выделенных штаммов вируса гриппа A / H1N1pdm09 показано наличие аминокислотных замен в гемагглютинине (рецептор-связывающем и Sa сайтах) и в генах, кодирующих внутренние белки (PA, NP, M1, NS1). Доля резистентных штаммов к препаратам с антинейраминидазной активностью в странах Северного полушария не превысила 1 %, а к производным адамантана оказались нечувствительными все изученные циркулирующие штаммы

SARS-CoV-2 Establishes a Productive Infection in Hepatoma and Glioblastoma Multiforme Cell Lines

Severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and rapidly caused a pandemic that led to the death of >6 million people due to hypercoagulation and cytokine storm. In addition, SARS-CoV-2 triggers a wide array of pathologies, including liver dysfunction and neurological disorders. It remains unclear if these events are due to direct infection of the respective tissues or result from systemic inflammation. Here, we explored the possible infection of hepatic and CNS cell lines by SARS-CoV-2. We show that even moderate expression levels of the angiotensin-converting enzyme 2 (ACE2) are sufficient for productive infection. SARS-CoV-2 infects hepatoma Huh7.5 and HepG2 cells but not non-transformed liver progenitor or hepatocyte/cholangiocyte-like HepaRG cells. However, exposure to the virus causes partial dedifferentiation of HepaRG cells. SARS-CoV-2 can also establish efficient replication in some low-passage, high-grade glioblastoma cell lines. In contrast, embryonal primary astrocytes or neuroblastoma cells did not support replication of the virus. Glioblastoma cell permissiveness is associated with defects in interferon production. Overall, these results suggest that liver dysfunction during COVID-19 is not due to infection of these tissues by SARS-CoV-2. Furthermore, tumors may potentially serve as reservoirs for the virus during infection

Cultivation of Cells in a Physiological Plasmax Medium Increases Mitochondrial Respiratory Capacity and Reduces Replication Levels of RNA Viruses

Changes in metabolic pathways are often associated with the development of various pathologies including cancer, inflammatory diseases, obesity and metabolic syndrome. Identification of the particular metabolic events that are dysregulated may yield strategies for pharmacologic intervention. However, such studies are hampered by the use of classic cell media that do not reflect the metabolite composition that exists in blood plasma and which cause non-physiological adaptations in cultured cells. In recent years two groups presented media that aim to reflect the composition of human plasma, namely human plasma-like medium (HPLM) and Plasmax. Here we describe that, in four different mammalian cell lines, Plasmax enhances mitochondrial respiration. This is associated with the formation of vast mitochondrial networks and enhanced production of reactive oxygen species (ROS). Interestingly, cells cultivated in Plasmax displayed significantly less lysosomes than when any standard media were used. Finally, cells cultivated in Plasmax support replication of various RNA viruses, such as hepatitis C virus (HCV) influenza A virus (IAV), severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and several others, albeit at lower levels and with delayed kinetics. In conclusion, studies of metabolism in the context of viral infections, especially those concerning mitochondria, lysosomes, or redox systems, should be performed in Plasmax medium