Day 2 :
Keynote Forum
Ilya B. Tsyrlov
XENOTOX Inc, USA
Keynote: A decade later, another look at what role in global spread of H5N1 played upregulation by host cell dioxin of gene encoding type A influenza virus NS1 binding protein
Time : 10:00 - 10:35
Biography:
Ilya B. Tsyrlov, M.D., Ph.D., D.Sci., has completed his PhD at the age of 27 years from Novosibirsk University and postdoctoral studies from Leningrad Academy of Medical Sciences. He is the President and Chief Scientific Officer of XENOTOX, Inc., an American premier biomedical innovation organization. He has published 4 monographs and about 250 papers in reputed journals and has been serving as an editorial board member of several jornals
Abstract:
Cognate DRE sites within DNA enhancer epitomizes wide range of mammalian genes expression mediated via the Ah receptor pathway. Earlier we postulated the same for DRE-containing viral genes transactivation caused by dioxin in human cells infected with HIV-1, HBV and HCMV. Here, such mechanistic concept applied to type A influenza virus NS1 binding protein in human and avian (G. gallus gallus) host cells. The NS1 is known to prevent transcriptional induction of antiviral interferons, to inhibit splicing and dsRNA-mediated signal transduction in target cells. Presenting data range from the cellular to population levels. It was shown that gene encoding the NS1 possessed multiple DREs (core nucleotide sequence 3' A-CGCAC 5'), two of which were identified within the promoter area, namely at positions -7942 and -687. SITECON, an established computational tool for detecting transcriptional factor binding site recognition, proved the above sites as potentially active. SITECON-selected adjacent variable sequences were used to detect properties of the DRE site, and conformational similiarity score threshold of 0.95 was utilized to rank identified DRE. On the cellular level, Western blot analysis of lysates of infected or DNA-transfected confluent HeLa cells pretreated with 10 ppt dioxin for 36 h revealed several-fold increase of NS1-specific polypeptide. As the NS1 promoter contains two potentially active DRE, an extrapolation from the data on HIV-1 (1 DRE) and HCMV (10 DRE) also suggests that concentration of dioxin upregulating NS1 gene should be moderately above current dioxin levels in general population (~ 4 ppt). Presumably, elevated dioxin level in the host cells might lead to enhanced ability of NS1 to diminish antiviral interferons. That can bring new insights to the fact that resistance of highly virulent H5N1 to antiviral effects of IFN-ß and TNF-alpha directly associated with the NS1. On the population level, the data on wild birds and domestic poultry (G. gallus gallus) dying from H5N1 in Guangdong province of China, and Long An, Tieng Giang and Ben Tre provinces of Vietnam, all relate to the fact that water and soil in these regions are highly contaminated with dioxin-like compounds. Eventually, human cohorts from the above regions of China and Vietnam are exposed to elevated concentrations of dioxin, which might serve as a promotional factor for seasonal influenza outbreaks. Moreover, the sub-nanomolar body burden dioxin might strongly facilitate spreading of the H5N1 in case avian flu pandemic were to occur.
Keynote Forum
Reza Nassiri
Michigan State University, USA
Keynote: Management and prevention of pandemic flu: One health approach
Time : 10:50 - 11:25
Biography:
Reza Nassiri is Associate Dean of Global Health; Director of Institute of International Health; Professor of Clinical Pharmacology, Professor of Family and Community Medicine, and lecturer in Global Health, Infectious Diseases and Tropical Medicine at Michigan State University College of Osteopathic Medicine. His research interests focuses on Clinical Pharmacology of HIV/AIDS & TB, prevention and control of infectious diseases, neglected tropical diseases, community health, global health, and socio-ethical determinants of health. Prof. Nassiri works on international public health issues and has expertise in global health education, research, policy and governance. He has made contributions in various fields of medical sciences including clinical investigation and health education. One the basis of his extensive experience and expertise in HIV/AIDS and TB, he developed Clinical Research Programs in Brazil, South Africa, Haiti, Dominican Republic and Mexico. The core foci of such programs are socio-cultural, bio-ethical determinant of HIV/AIDS and TB prevention, control, and intervention.
Abstract:
About 75 recently emerging infectious diseases that affect humans are caused by various zoonotic pathogens including influenza viruses such as H1N1, H5N1, and H7N9. Pandemic influenza outbreaks significantly highlights about the role of One Health (OH) approach where expertise in human, animal, and environmental health combines together with multidisciplinary strategies solve interrelated problems to adapt effective collaboration, communication, management and evidenced-based preventive measures. Avian and Swine flu are examples of global health concern that justify exploring the role of OH enhancing optimal preventive outcome and to promptly disseminate epidemiologic data sharing among various stakeholders including academic institutions that are traditionally well equipped to collaborate with the internal and external stakeholders, especially in areas such as human, veterinary, and laboratory surveillance practices. The human-animal-ecosystem interface plays a critical role in spread of emerging and re-emerging infectious disease including influenza viruses. As the world population is rising especially urban populations, we are facing an increase in poultry and swine populations globally by necessity, and therefore, increased in the frequency of zoonotic influenza viruses’ infections among human populations is more likely. One Health approach which is formulated to mitigate and curb public health best practice for the triple threats, can result in direct benefits in human health. Furthermore, adaptation and incorporation of such approach will significantly impact preventive measures as well as identification of risk factor and risk assessment. Major health organizations, such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), the US Institute of Medicine (IOM), and the European Centers for Disease Control have unanimously concluded that that more action and information on influenza transmission and prevention is internationally critical to pandemic planning and management. Human health is directly and inextricably linked to the health of animals and ecosystem and influenza viruses are no exception to this pivotal link. One Health collaborations and implementations can help to effectively minimize the burden of disease including economic burden. Therefore, improving international public health infrastructure for zoonotic disease control and prevention through OH approach provides advantages and benefits in controlling zoonotic diseases caused by influenza viruses.
- Track 2:Pathogenicity of Influenza Virus Track 4:Global Market for Influenza Vaccine Manufactures Track 6:Antiviral Drug Development and Treatment Strategies, Including Vaccination Track 10:Influenza Lung Immunology: Major Aspects Track 11:Animal Flu-Ecology
Chair
Reza Nassiri
Michigan State University, USA
Co-Chair
Hanna Radecka
Polish Academy of Science, Poland
Session Introduction
Tatyana Ilyicheva
Vector State Research Center of Virology and Biotechnology, Russia
Title: Influenza in Russia in 2014-2016
Time : 11:25-11:50
Biography:
Tatyana Ilyicheva has completed her PhD at the age of 33 years from Lobachevsky State University of Nizhni Novgorod and postdoctoral studies from Vector State Research Center of Virology and Biotechnology. She is the head of influenza laboratory of Vector Center and associated professor of Novosibirsk State University. She has published more than 20 papers in reputed journals.
Abstract:
In 2014–2015, fifteen influenza A(H3N2), two A(H1N1pdm09), and one B (Yam) virus strains were isolated from autopsy and clinical material from individuals with severe course of influenza-like disease. In 2015–2016, we isolated 105 influenza A(H1N1pdm09), one influenza A(H3N2) viruses from autopsy material, and 226 influenza A(H1N1pdm09) and four influenza A(H3N2) viruses from nasopharyngeal swabs. Virus A/Khabarovsk/6/2015 (H3N2) showed reduced sensitivity to oseltamivir (18-fold below normal). All other viruses exhibited normal inhibition by oseltamivir and zanamivir. Ð(H1N1pdm09) viruses were antigenically characterized as A/California/07/2009-like. Their HA gene sequences fell into genetic group 6B, the predominant genetic group. H3N2 isolated viruses were characterized as A/Hong Kong/4801/2014-like and A/Switzerland/9715293/2013-like, their HA gene sequences belong to genetic groups 3C.2a and 3C.3a, respectively. Influenza B virus was antigenically similar to B/Phuket/3073/2013, its HA sequence belongs to genetic group Y3. In 2014, we isolated influenza A(H5N8) virus from a Eurasian wigeon (Anas penelope) in Eastern Siberia. The strain A/wigeon/Sakha/1/2014 (H5N8) was shown to be pathogenic for mammals. It is similar to the strains that caused outbreaks in wild birds and poultry in Southeast Asia and Europe in 2014. In spring 2015, we isolated tree influenza A(H5N1) viruses from wild birds in the South of Western Siberia. All strains were pathogenic for mammals and showed reduced anti-neuraminidase drug sensitivity. In total 3,888 human blood serum samples were collected in October–November, 2014 in Russia. The presence of antibodies to influenza viruses in the sera was tested in hemagglutination inhibition test. None of the samples produced positive results with influenza A(H5N1), A(H5N8), and A(H7N9) viruses.
Melia Magnen
Institut National de la Santé et de la Recherche Médicale, France
Title: Kallikrein-related peptidase 5 contributes to H3N2 influenza virus infection in human lungs
Time : 11:50-12:15
Biography:
Melia Magnen is currentlypersuing her PhD at the CEPR, Tours, France.
Abstract:
The cleavage of the influenza A virus hemagglutinin (HA) by host serine-proteases is essential for viral infectivity. Several serine proteases of the kallikrein-related peptidase (KLK) family are produced and secreted by the airways and we investigated whether KLK1, 5 and 14 were involved in seasonal IAV infection. Expression of KLK1, 5 and 14 was assessed at the protein levels, in human tracheal aspirates from flu patients in intensive care unit, using ELISA. Primary human bronchial epithelial cells (hBEC) cultured at the Air-liquid interface were infected with IAV and the expression of KLKs was analyzed by RT-qPCR and flow cytometry. We also investigated in vitro if KLK1, 5 and 14 were able to cleave HA precursors. Finally, inactivated virions (mouse adapted A/Scotland20/74, H3N2) were treated with KLKs and the infectiveness was determined in MDCK cells and in mice. Flu infection selectively increased expression of KLK5 in hBEC and its secretion in the human airways. KLK1, 5 and 14 were able to cleave in vitro HA precursor from several subtypes of influenza viruses. Furthermore, only the KLK5 treatment of H3N2 virions promoted IAV infection in MDCK cells. In mice, the treated virus led to severe infection with KLK5 treatment and to moderate one with KLK14 treatment. KLK1 virus treatment did not result in infection. Expression and secretion of KLK5 is specifically induced in airways upon flu. This induction likely contributes to the propagation of the virus in favoring its multi-cycle replication through activation of the HA precursor.
Essam Badawy
Minia University, Egypt
Title: The clinical characteristics and outcome of H1N1 pneumonia patients with and without acute renal injury
Time : 12:15-12:40
Biography:
Essam Badawy has completed his MD at the age of 34 years from Minia University, EGYPT and ITS THESIS studies from Cairo University School of Medicine. He is the director of Emergency Department, Hera General Hospital, JCI-Accredited governmental hospital, MOH, KSA. He is senior consultant Internal Medicine & professor of Internal Medicine & Immunology, Faculty of Medicine, Minia University. He has published more than 24 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Currently, little information exists about the impact of kidney injury and resource utilization in the form of renal replacement therapy in critically ill patients with H1N1 infections. 40 patients who were living inor visitors to Makkah region , admitted to the hospital and revealed confirmatory H1N1 infection, pneumonia and acute renal injury, were submitted to rRT-PCR. Severity of illness was assessed by using APACHE II, SOFA score, MOD score XR Chest score, PaO2/FIO2 and Co-morbidities were recorded. Acute renal injury is an adding impact of increasing the mortality rate of H1N1 pneumonia patients and may be related directly to the infection by this virus or complication to it which may be explained by severe hypoxia secondary to severe lung injury , multiorgan dysfunction. A high mortality in middle and old- aged patients with underlying medical co-morbidities was associated with higher symptoms severity, APACHE II, SOFA, MODS and XRC scores. Early recognition of the disease as well as prompt medical attention to provide opportunities aiming to limit the progression of the illness and to reduce the mortality. Prospective and controlled clinical trials are needed for claryfing the effectiveness of the early treatment and protection by using H1N1 vaccine.
Biography:
De-chu Christopher Tang is the Founder of VaxDome LLC and Vaxin Inc. (Vaxin’s nameplate was changed to Altimmune, Inc. in 2015 after merging with Immune Targeting Systems Ltd). He obtained his PhD in Microbiology from Indiana University in 1989. He carried out his postdoctoral work at Baylor College of Medicine, Duke University, and University of Texas Southwestern Medical Center. He joined the faculty at University of Alabama at Birmingham (UAB) in 1994; subsequently founded Vaxin Inc. on UAB campus in 1997; and was responsible for Vaxin’s daily operation as the Chief Scientific Officer until 2012. Dr. Tang was one of the pioneers during the development of DNA vaccines, noninvasive skin-patch vaccines, adenovirus-vectored nasal vaccines, adenovirus-vectored poultry vaccines, as well as the protective innate-adaptive immunity duo platform technology. He received the Wallace H. Coulter Award for innovation and entrepreneurship in 2000; and Vaxin Inc. was selected as a Tech Museum Awards Laureate in 2007. Dr. Tang was selected as a Distinguished Overseas Scientist by the South Korea KOFST Brain Pool Program in 2012; subsequently joined Chung-Ang University and International Vaccine Institute (IVI) in Seoul; and was appointed as a Scientist at IVI after the Brain Pool Program Award expired in 2013. He founded VaxDome LLC in Birmingham, Alabama, USA in 2014 and moved the company to Dallas, Texas, USA in 2015.
Abstract:
We report that intranasal administration of an E1/E3-defective (ï„E1E3) adenovirus serotype 5 (Ad5)-vectored influenza vaccine could induce seroconversion in human volunteers without appreciable adverse effects, even in subjects with pre-existing Ad5 immunity. Mice and ferrets were well protected against challenge by a lethal dose of an H5N1 avian influenza virus following intranasal instillation of an Ad5 vector encoding hemagglutinin (HA) in a single-dose regimen. Moreover, the ï„E1E3 Ad5 particle itself without transgene could confer rapid-sustained-broad protection against influenza by inducing an anti-influenza state in a drug-like manner, conceivably by activating a specific arm of innate immunity. An Ad5 vector encoding HA thus consolidates drug and vaccine into a single package, which allows the Ad5 backbone to induce protective innate immunity capable of conferring nearly-immediate and prolonged (e.g., 5 hours to 47 days) protection as the first wave against influenza; followed by HA-mediated adaptive immunity as the second wave before the innate immunity-associated anti-influenza state declines away. Overall, the work conceivably would foster the development of a novel noninvasive drug-vaccine duo platform technology capable of conferring rapid-sustained-broad protection in a wide variety of influenza settings, with neither the potential to induce drug resistance nor that to trigger harmful systemic inflammation.
Jacob A Dunga
ATBU Teaching Hospital, Nigeria
Title: Types of human influenza virus among patient at Abubakar Tafawa Balewa University Teaching Hospital (ATBUTH), Bauchi, Nigeria
Time : 12:40-13:05
Biography:
Jacob A Dunga has completed his MBBS at the age of 24 years from University of Maiduguri Teaching Hospital, Borno state and postgraduate fellowship in Pulmonology at National postgraduate medical college of Nigeria. He also has postgraduate diploma in management and master’s degree in health planning and management. He is senior consultant Physician (Pulmonologist) at ATBU Teaching Hospital and a visiting senior lecture with Gombe state University medical college. He is a member of ATS, ERS, PATS, and NTS. He has published more than 10 papers and has served as research coordinator for National Influenza surveillances and PMTCT
Abstract:
Human influenza is an acute respiratory illness resulting from infection with an influenza virus, it is ahighly infectious virus and can spread rapidly from person to person,and some strains are more pathogenic than others. Nigeria suffered waves of Highly Pathogenic Avian Influenza (HPAI) outbreaks that peaked twice in February 2006 and February 2007.The burden of Influenza is likely to be under estimated in Nigeria. This study is expected to monitor the occurrence of influenza in this part of the country, with the aim of providing a foundation for detecting outbreaks and pandemics, mapping out common strains or emergence of a novel strain of influenza so as to create an early warning system to trigger a rapid public health response and specific vaccine for common strains.This study is a cross sectional survey, our target populations were all adult and pediatric patient admitted at the pediatrics and internal medicine department of ATBUTH who has met the criteria for Cough, fever (>37 o C), nasal congestion and dyspnea. Samples collected over 12 months were analyzed using the polymerase chain reaction (PCR) at national influenza reference laboratory (NIRL).Detection and subtyping of influenza viruses in respiratory specimens was done. Overall 49% female samples and 51% males samples were collected, 5% of the samples collected tested positive for human influenza type A and B, 60% of the positive result were among the female samples where as 40% from the male samples, among the positive sample about 80% were positive for Human Influenza type A (Flu A), whereas 20% where positive for Human Influenza type B (Flu B). There were more cases of human influenza among the age group 1 - 5years equals 3% of total samples collected compared to 1% each for 6 – 25years and 26 – 45years, the incidence were found to be less or absent among those > 45years.
Nailya Klivleyeva
Institute of Microbiology and Virology, Kazakhstan
Title: Study on the circulation of influenza A virus in swine populations in Kazakhstan
Time : 13:50-14:15
Biography:
Nailya Klivleyeva is presently working in Institute of Microbiology and Virology, Kazakhstan.
Abstract:
Emergence of influenza virus A (H1N1)pdm in humans which is a complex reassortant of the swine-origin genotypes, emphasized the importance of worldwide surveillance for influenza virus in swine. 1293 biosamples (893 nasopharyngeal swabs and 400 blood serums) have been collected from swine in the small and large pig farms of the Almaty, Aktobe, Karaganda, Kostanaу, Pavlodar and North-Kazakhstan oblasts in 2014-2015. Primary screening of 893 biosamples (nasopharyngeal swabs), carried out in RT-PCR using AmliSens PCR test system produced by the Central Research Institute for Epidemiology (Moscow) showed the presence of genetic material of the influenza virus in 171 samples (19.15% of the total number of examined samples). Influenza A/H1 virus RNA was detected in 111 samples (12.43%), A/H3 virus RNA - in 10 samples (1.12%). These data indicate circulating influenza virus of mixed etiology in the swine population with a predominance of influenza Ð/Ð1 virus. As a result of primary infection of chicken embryos with 893 biosamples collected from swine in various regions of Kazakhstan, 22 infectious agents were isolated with the hemagglutination titres of 1:2-1:32 and infectious activity of 3.47-9.45 lgEID50/0.2ml. Identification in HAI and NAI assays of seven isolates from the Almaty (06/14 and 10/14), Karaganda (04/14 and 16/14) and Kostanaу (12/14, 23/14 and 24/14) oblasts enabled to attribute them to influenza A virus with the H1N1 antigenic formula. Serological analysis of 400 blood serums collected from healthy and sick swine in the pig-breeding farms to detect antibodies against influenza A/H1N1 and A/H3N2 virus was carried out with IEA and HAI assay. The greatest number of specific antibodies was detected against the influenza virus subtype A/H1N1.Thereby, the findings confirm the circulation of influenza Ð/Ð1N1 virus in the swine population on the territory of Kazakhstan, which indicates the need for a permanent virological examination of swine with the aim of the earliest detection of the potential pandemic influenza virus strain.
Mohammad Ali Daneshmehr
Iran University of Mediccal Sciences, Iran
Title: Herbal immune boosters: Valuable preventive means for international travelers flu
Time : 14:15-14:40
Biography:
Mohammad Ali Daneshmehr has studied pharmacy at Tehran University of Medical Sciences (TUMS), and graduated in 1990. He started career in Shahid Beheshti University of Medical Sciences (SBMU) as an instructor. In 1993 he pursued his studies in University of Manchester, UK in medicinal chemistry and got PhD (2001) on ligands in DNA minor groove. He has been working since, in different parts of Iran as founder of a number of pharmacy schools including Hamadan (UMSHA), Kermanshah (KUMS) and currently Iran University of medical Sciences (IUMS). Fields of interests includes natural products as lead compounds to find new drugs.
Abstract:
Acute respiratory tract infections are account for millions of lost effective work or school days, healthcare clinic visits, antibiotic prescriptions, hospital admissions and eventually morbidity or even mortalities. International tourism including religious pilgrimage to overcrowded destinations considerably increases the chance for dissemination of such contaminations. As an example, Hajj is a world wide ceremony that can affect every country with Muslim sub-population regarding surge of multi-microbial and drug resistant respiratory tract infections. Therefore disease prevention in the involved societies would be highly life and cost saving. Besides use of common antibiotics that has major drawbacks, natural immune boosters are viable and accredited options in this field. Echinacea supplements are well-known for immune-modulation and anti-flu effects. They have all characteristics that recommended by CDC to fight flu: immune augmentation, evidence-based preventive value and anti-viral (microbial) properties without promoting any resistance or life-threatening adverse reactions. Echinacea vastly grows in different geographical teritories, is reasonably affordable and easily accessible almost all over the world just like in Iran. As we published in a recent review article, there is a huge amount of evidence that shows promising results for Echinacea in both prevention and treatment of respiratory tract infections especially in high risk populations and would be potentially useful in susceptible travelers. There will be a great opportunity to prevent respiratory tract infections related to international gatherings and their infectious adverse consequenses with standard protocls for supplementation of natural products like Echinacea after adequate examinations via goal-directed clinical trials.
Anil kumar Prasad
Indian Virological Society, India
Title: Influenza prevention essential in developing countries
Biography:
Anil kumar Prasad is the currently working as President of Indian Virological Society.He is also the chairman of Influenza Foundation of India.He was elected Fellow of the Geriatric Society of India (FGSI) 2014 at their Nagpur Convention (8-9 November, 2014).He has also Published over 60 Research Papers in national & International Journals & 3 Books (Chapter on Influenza).He has also received Life Time Achievement Award conferred by the Geriatric Society of India on 06th November, 2014 at the Vaccine Advocacy for the S E Asian Countries held at Delhi.
Abstract:
TBA
Chiek J. Er
Norwegian Veterinary Institute, Norway
Title: Occurrence and spread of influenza A(H1N1)pdm09 virus infection in Norwegian pig herds based on active serosurveillance from 2010 to 2014
Biography:
Chiek Er has been a veterinary epdidemiologist with the Norwegian Veterinary Institute since 2007. His current research activities focus on the epidemiological aspects of influenza A(H1N1)pdm09. Since 2009, he has coauthored 7 published articles on influenza A(H1N1)pdm09. He is first author for the three latest ones.
Abstract:
The incursion of influenza A(H1N1)pdm09 virus was detected by Norway’s active serosurveillance of its pig population in 2009. Since then, surveillance data from 2010 to 2014 revealed that 54% of 5643 herd tests involving 1567 pig herds and 28% of 23 036 blood samples screened positive for antibodies against influenza A virus. Positive herds were confirmed to have influenza A(H1N1)pdm09 virus infection by haemagglutination inhibition test. In 50% of positive herd tests, 560% of the sampled pigs in each herd had antibodies against influenza A(H1N1) pdm09 virus. This within-herd animal seroprevalence did not vary for type of production, herd size or year of test. The overall running mean of national herd seroprevalence, and annual herd incidence risks fluctuated narrowly around the means of 45% and 32%, respectively, with the highest levels recorded in the three densest pig-producing counties. The probability of a herd being seropositive varied in the five production classes, which were sow pools, multiplier herds, conventional sow herds, nucleus herds, and fattening herds in descending order of likelihood. Large herds were more likely to be seropositive. Seropositive herds were highly likely to be seropositive the following year. The study shows that influenza A(H1N1)pdm09 virus is established in the Norwegian pig population with recurrent and new herd infections every year with the national herd seroprevalence in 2014 hovering at around 43% (95% confidence interval (40–46%).
Hany Khalil
University of Sadat City, Egypt
Title: Novel and efficacious compounds disturb influenza A virus infection
Biography:
Hany Khalil has completed his PhD at the age of 35 years from Humboldt University in collaboration with Max-Planck Institute for Infection Biology followed by 6 months postdoctoral fellowship at Max-Planck Institute for Infection Biology, Berlin, Germany . Additional 4 months postdoctoral fellowship at Wexner Medical Research Center, Ohio State University, USA. He is the Assistant Professor at Genetic Engineering and Biotechnology Research Institute, Department of Molecular Biology, University of Sadat City Egypt. He is Principle Investigator in Two different projects supported by (STDF) projects ID,6117 and project ID, 4694.
Abstract:
Influenza A virus is a negative RNA stranded virus of the family Orthomyxoviridae, and represents a major public health threat, compounding existing disease conditions. Influenza A virus replicates rapidly within its host and the segmented nature of its genome facilitates re-assortment, whereby whole genes are exchanged between influenza virus subtypes during replication. Antiviral medications are important pharmacological tools in influenza virus prophylaxis and therapy. However, the use of currently available antiviral is impeded by sometimes high levels of resistance in circulating virus strains. Notably, the over use of existing antiviral drugs such as oseltamivir (Tamiflu) and zanamavir (Relenza) increases the likelihood of viral escape mutations. Here, we identified novel anti-influenza compounds through screening of chemical compounds that synthesized de novo and several naturally occurring products on human lung epithelial cells. Computational and experimental screening of extensive natural products and water soluble chemical compounds identified novel influenza virus inhibitors that can reduce influenza virus infection without any detectable toxic effects on host cells. Interestingly, the indicated active chemical compounds inhibit viral replication most likely via interaction with cell receptors and disturb influenza virus entry into host cells. Additionally, the selected natural product inhabits viral replication via increasing of interferon beta (IFN-β) production from infected cells. In conclusion, screening of new synthesis compounds and natural extractions on influenza A virus replication provides a novel and efficacious anti-influenza compounds that can inhibit viral replication and indicates that these compounds are attractive candidates for evaluation as a potential anti-influenza.
Jehan El Kholy
Cairo University Hospital, Egypt
Title: Burden of acute lower respiratory tract infection caused by influenza virus among children in Egypt
Biography:
Jehan El Kholy is a Professor of Anesthesia and Intensive Care who works as a Deputy Director of Cairo University Hospitals since 2013. She is a certified Infection Prevention and Control Specialist and she is responsible for preparedness and response to influenza and other infections in a teaching hospital that plays a role model among all Egyptian hospitals in collaboration with Naval Medical Research Unit, No.3 (NAMRU-3). She was awarded by the Egyptian Minister of Health to be the Best Leader Implementing Active Surveillance of Influenza and healthcare- associated infections in Cairo University Hospitals.
Abstract:
Background: Influenza virus is one of the most important causes of acute lower respiratory tract infections (ALRTI) in children. We aimed to assess the burden of influenza among hospitalized children less than 5 years in Egypt. Methods: We enrolled 3075 patients, of which 77.8% were children less than 5 years old diagnosed with ALRTI admitted to Cairo University Hospitals during five-year period from 2010 to 2014. Nasopharyngeal aspirates were obtained from the patients and tested for influenza among 16 respiratory viruses by mutliplex PCR. Results: Patients had a mean age of 4 months, 53.4% were males. Average hospitalization duration was 5 days, 35% were positive for one or more virus. Influenza A and influenza B were detected in 6.2% and 3.2% of children respectively. All influenza patients presented with cough and fever. More than 80% had tachypnea and nasal flare. Complications were associated with chronic lung and heart conditions. The most common complications were ARDS (81.8%), requiring ICU admission (12%) and death in 8.2%; though seasonal distribution was not consistent, yet 80% of influenza cases occurred in winter and early spring seasons (p<0.001). Nosocomial transmission occurred in 2 outbreaks in a Surgical Pediatric Intensive care units, affecting 7 children. Conclusion: Influenza is an important etiology of ALRTI in children below 5 years of age. As it is more prevalent in winter and tends to cause severe infection in high risk group, vaccination, rapid diagnosis and early start of antiviral therapy are essential.
Melia Magnen
Institut National de la Santé et de la Recherche Médicale, France
Title: Kallikrein-related peptidase 5 contributes to H3N2 influenza virus infection in human lungs
Biography:
Melia Magnen is currentlypersuing her PhD at the CEPR, Tours, France.
Abstract:
The cleavage of the influenza A virus hemagglutinin (HA) by host serine-proteases is essential for viral infectivity. Several serine proteases of the kallikrein-related peptidase (KLK) family are produced and secreted by the airways and we investigated whether KLK1, 5 and 14 were involved in seasonal IAV infection. Expression of KLK1, 5 and 14 was assessed at the protein levels, in human tracheal aspirates from flu patients in intensive care unit, using ELISA. Primary human bronchial epithelial cells (hBEC) cultured at the Air-liquid interface were infected with IAV and the expression of KLKs was analyzed by RT-qPCR and flow cytometry. We also investigated in vitro if KLK1, 5 and 14 were able to cleave HA precursors. Finally, inactivated virions (mouse adapted A/Scotland20/74, H3N2) were treated with KLKs and the infectiveness was determined in MDCK cells and in mice. Flu infection selectively increased expression of KLK5 in hBEC and its secretion in the human airways. KLK1, 5 and 14 were able to cleave in vitro HA precursor from several subtypes of influenza viruses. Furthermore, only the KLK5 treatment of H3N2 virions promoted IAV infection in MDCK cells. In mice, the treated virus led to severe infection with KLK5 treatment and to moderate one with KLK14 treatment. KLK1 virus treatment did not result in infection. Expression and secretion of KLK5 is specifically induced in airways upon flu. This induction likely contributes to the propagation of the virus in favoring its multi-cycle replication through activation of the HA precursor.