Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 2nd International conference on Flu San Francisco, California, USA .

Day 2 :

Keynote Forum

Phillip B. Berkey Moheno

SanRx Pharmaceutical Inc, USA

Keynote: Calcium folate for flu prevention and control

Time : 09:30 - 10:05

OMICS International Flu-2016 International Conference Keynote Speaker Phillip B. Berkey Moheno photo
Biography:

Phillip B. Berkey Moheno holds a BS and a Candidate in Philosophy in Biochemistry from the University of California, Los Angeles, and a PhD in Confluent Education from the University of California, Santa Barbara. In addition he has more than 20 years of research experience into the anti-cancer properties of pterins. He has published 12 papers in reputed journals.

Abstract:

Calcium Folate is the excess calcium salt of the vitamin folic acid. Folic acid is sensitive to acidic-oxidative conditions and, in the presence of excess Ca+2 as well, is transformed into pterins and calcium pterins. This pilot observational study describes the use of CaFolate-derived calcium pterin 6-carboxylate in the treatment of certain immune-related ailments. Patients with various immune-associated disorders were directed to take ad libitum 25-76 mg of CaFolate (300-900 µg folic acid equivalent) orally per day, as an adjuvant therapy, and to collect personal and medical assessments. The users reported no flu/colds (>20/20 reporting none during the cold and flu season), greater energy/stamina (8/8 reporting increased), less osteoarthritis pain (10/11 reporting improvement), diminished mouth sores due to chemotherapy (2/2 reporting significant clearance), and cancer remissions (4/5 reported plus 1 transient improvement in a terminal case). These observational findings identify certain clinical endpoints for future matched group, randomized, double-blind, placebo-controlled clinical trials. One such clinical trial is underway in osteoarthritis.

OMICS International Flu-2016 International Conference Keynote Speaker Sunil K. Lal photo
Biography:

Sunil K. Lal joined the School of Science, Monash University, Malaysia in 2014. By training, Prof. Sunil is a PhD in Microbial Genetics from Georgia Institute of Technology, Atlanta (USA) in 1989 following which he was appointed Faculty at the California Institute of Technology, Pasadena (USA). In 1994 Prof. Sunil joined as a Senior Research Scientist at the International Centre for Genetic Engineering & Biotechnology (ICGEB), New Delhi where he worked for 22 years. Prof. Sunil is internationally well known for his research work in the field of Tropical and Infectious Disease Biology. He has been a visiting scientist to Universiti Malaysia Sarawak, National University of Singapore, Karolinska Institute, Sweden and the Centers for Disease Control (CDC) Atlanta.

Abstract:

Sporadic outbreaks of epizootics like SARS coronavirus and H5N1 avian influenza remind us of the potential for communicable diseases to quickly spread into worldwide epidemics. Despite improved surveillance and quarantine measures, we find ourselves under the threat of swine-flu, bird-flu and a pandemic at any time. Effective and new therapeutic targets are essential to protect against current and future pandemics and the best route to achieving this is through a detailed and global view of virus–host interactions. Here, we provide our perspective on the role of virus-host interactions in deepening our understanding of the scope for the discovery of new anti-viral targets.To prepare for future influenza outbreaks, it is necessary to understand how the virus interacts and manipulates the host pathways and to determine what makes certain strains of influenza highly pathogenic. Functional genomics provides a unique approach to this effort by allowing researchers to examine the effect of influenza infection on global host mRNA levels. Biological validation of such novel predictions and the use of screens to identify new virus-host interactions has been our approach to identifying potentially new anti-viral targets. We have deployed a variety of experimental systems that allow current models to be refined and thus provide us the basis for further predictions and hypothesis generation. By examining these changes in a comprehensive manner, we have been able to discover exciting new insights into innate immunity, cytokine and cell signaling, cell survival, death and proliferation thus shedding new vision on strategies used by influenza viruses to overcome these cellular barriers.

  • Track 2: Pathology of Influenza Virus Infections Track 3: Flu Symptoms & Treatment Track 5: Flu Clinical Studies & Case Reports Track 6 : Antivirals and Therapeutics Track 11 : Epidemiology and Public Health of Influenza
Location: San Francisco, USA

Session Introduction

Phillip B. Berkey Moheno

SanRx / CSU USA

Title: Calcium folate for flu prevention and control
Speaker
Biography:

Phillip B. Berkey Moheno holds a BS and a Candidate in Philosophy in Biochemistry from the University of California, Los Angeles, and a PhD in Confluent Education from the University of California, Santa Barbara. In addition he has more than 20 years of research experience into the anti-cancer properties of pterins. He has published 12 papers in reputed journals.

Abstract:

Calcium Folate is the excess calcium salt of the vitamin folic acid. Folic acid is sensitive to acidic-oxidative conditions and, in the presence of excess Ca+2 as well, is transformed into pterins and calcium pterins. This pilot observational study describes the use of CaFolate-derived calcium pterin 6-carboxylate in the treatment of certain immune-related ailments. Patients with various immune-associated disorders were directed to take ad libitum 25-76 mg of CaFolate (300-900 µg folic acid equivalent) orally per day, as an adjuvant therapy, and to collect personal and medical assessments. The users reported no flu/colds (>20/20 reporting none during the cold and flu season), greater energy/stamina (8/8 reporting increased), less osteoarthritis pain (10/11 reporting improvement), diminished mouth sores due to chemotherapy (2/2 reporting significant clearance), and cancer remissions (4/5 reported plus 1 transient improvement in a terminal case). These observational findings identify certain clinical endpoints for future matched group, randomized, double-blind, placebo-controlled clinical trials. One such clinical trial is underway in osteoarthritis.

Donald Pinkston Francis

Global Solutions for Infectious Diseases, USA

Title: Dramatic changes in the development and supply of vaccines for the world

Time : 10:55 - 11:20

Speaker
Biography:

Donald Pinkston Francis, completed undergraduate studies at the U.C. Berkeley, received his M.D. from Northwestern University and his Doctor of Science in Virology from Harvard. He joined CDC in the early 1970s, where combated smallpox, cholera, Ebola and AIDS. His early work on HIV/AIDS was chronicled in Randy Shilts? And the Band Played On. From 1988 to 1992, he was Special Consultant on AIDS to San Francisco Mayor Art Agnos. After retiring from CDC in 1992 he worked on HIV vaccines at Genentech, VaxGen and now a not-for-profit company GSID.

Abstract:

In recent years, there have been dramatic changes in both the supply of existing vaccines and early stage development of new vaccines. There have been shifts that have seen vaccine companies from Brazil, India and China taking larger and larger roles in both the development and production. From the vaccine production/supply side, companies from emerging markets supplied less than 10% of UNICEF purchased vaccines in 1997. That increased to about 50% by 2012. From the vaccine development side, some of these companies have undertaken major projects for the development of new products for diseases as disperate as malaria, dengue, human papiloma virus, influenza and Japanese encephalitis. The movement of these vaccines from early development, to local licensure and then to UNICEF prequalification, bodes well for the health of the world.

Shan Lu

University of Massachusetts Medical School, USA

Title: TBA
Speaker
Biography:

Shan Lu is professor of medicine and biochemistry & molecular pharmacology, has been elected president of the International Society for Vaccines (ISV). He is a physician-scientist, is a pioneer in the field of DNA vaccines and has conducted extensive research on AIDS vaccines, as well as vaccines against emerging infectious disease and biodefense targets.

Abstract:

TBA

Nicolas Noulin

hVIVO, UK

Title: TBA
Speaker
Biography:

Nicolas Noulin has completed his PhD in Immunology and Molecular Biology from Orleans University (France) and Post-doctoral studies from Institut Pasteur in Paris. He is a Principle Virologist at hVIVO, a company pioneering a technology platform which uses human models of disease.

Abstract:

TBA

Tony Velkov

Monash University, Australia

Title: Hemagglutinin receptor binding specificity of H10N7 avian influenza

Time : 11:20-11:45

Speaker
Biography:

Tony Velkov has completed his PhD from Monash University, Australia in 2000. His research focus is in the field of anti-infective discovery. He was awarded a National Health and Medical Research Council (NHMRC) Research Fellowships in 2006, 2011 and 2015. The quality and impact of his independent research was recognized by the NHMRC with an Excellence Awards in 2011 and 2015. He has published over 70 papers in high caliber journals and 5 book chapters.

Abstract:

Influenza is a constant global burden to human health. In order to evolve from its avian form and gain the pandemic potential for increased transmissibility between humans, the hemagglutinin (HA) of avian influenza viruses will need to undergo mutations in its receptor binding site (RBS) that bring about an avian to human receptor preference switch. In order to understand the major determinants of virus transmissibility and the pandemic potential of the novel avian influenza viruses we have determined the crystallographic structure of the novel avian influenza H10N7 A/Turkey/MN/3/79 to 1.96Å and mapped the RBS. The amino acid residues responsible for conferring receptor selectivity were identified by site direct mutagenesis of recombinant H10 HA proteins. The receptor binding selectivity of the HAs was determined using sialyl glycan binding assays. Docking models were constructed of the H10 HA in complex with α2,6-sialic acid (human) and α2,3-sialic acid (avian) pentasaccharide receptor analogs to ascertain the correlation between the binding assay data and the interactions within the receptor binding pocket. The presented findings provide a structure recognition perspective for the receptor binding properties of the novel avian H10 influenza HA.

Speaker
Biography:

Zheng Li has completed his PhD at the age of 31 years from Xi'an Jiaotong University and postdoctoral studies from German Cancer Research Center. He has published more than 27 papers in reputed journals in the last five years.

Abstract:

Recent studies have elucidated that expression of certain glycoproteins in human saliva are increased or decreased according to age, meanwhile, human saliva may inhibit viral infection and prevent viral transmission. We find that seven lectins (e.g., MAL-II and SNA) show significant age differences among children, adults, and elderly individuals. Interestingly, we observe that healthy elderly individuals have the strongest resistance to influenza A virus mainly by presenting more terminal α2-3/6-linked sialic acid residues in their saliva, which bind with the influenza viral hemagglutinations. However, it is often noted that hospitalizations and deaths after an influenza infection mainly occur in the elderly population living with chronic diseases, such as diabetes and cancer. We find that the expression level of the terminal α2-3-linked sialic acids of elderly individuals with type 2 diabetes mellitus and liver disease are down-regulated significantly, and the terminal α2-6 linked sialic acids are up-regulated slightly or had no significant alteration. But, in the saliva of patients with gastric cancer, neither sialic acid is significantly altered. These findings may reveal that elderly individuals with chronic diseases, such as diabetes and liver disease, might be more susceptible to the avian influenza virus due to the decreased expression of terminal α2-3-linked sialic acids in their saliva.Our findings imply that the expression level of terminal α2-3 or α2-6-linked sialic acids in human saliva is a risk factor that could be a biomarker to distinguish those patients who are at a greater risk for infection with the avian or human influenza viruses.

Speaker
Biography:

Wen Tian Chen has completed his PhD from Northwest University in China. He is a Lecturer in Northwest University. He has published more than 5 papers in reputed journals.

Abstract:

We undertook a detailed investigation of the distribution and the evolutionary pattern of the potential glycosites (N-glycosylation site) in the envelope glycoproteins of Influenza Virus. Two glycosites were located at HA0 cleavage sites (e.g., the 27N in H1) and fusion peptides (e.g., the 498N in H1) and were strikingly conserved in all HA subtypes. Two to four conserved glycosites were found in the stalk domain of NA, but these are affected by the deletion of specific stalk domain sequences. Another highly conserved glycosite (e.g., the 146N in N2) appeared at the top center of tetrameric global domain, while the others glycosites were distributed around the global domain. We further focus on the H5N1 virus and conclude that the glycosites in H5N1 have become more complicated in HA and less influential in NA in the last seven years. Two glycosylation sites, 158N and 169N, which located near to the receptor-binding domains (RBDs) of HA, also participated in receptor recognition. We attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA(Sialic Acid)-a-2,3-Gal(Galactose) and SA-a-2,6-Gal sialoglycan adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-a-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-a-2,3-Gal analogs.

Speaker
Biography:

Ilya B Tsyrlov has completed his PhD 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 journals.

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 similarity 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 up-regulating 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-β and TNF-α 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.

Diane Beylkin

SRI International, USA

Title: Targeting the influenza RNA-dependent RNA polymerase

Time : 12:10-12:35

Speaker
Biography:

Diane Beylkin graduated with honors from Caltech in 2010 with a B.S. in chemistry. She recently completed her PhD at Yale University in the laboratory of Dr. Andrew Phillips working on the total synthesis of thailandamide A. She is currently conducting her postdoctoral research on the influenza virus at SRI International in the laboratory of Dr. Thomas Webb.

Abstract:

Influenza is an infectious disease responsible for up to 500,000 deaths worldwide annually despite the availability of vaccines and antiviral drugs. Vaccines target the most common strains of the virus, leaving those exposed to other strains at risk for infection. Most small molecule antiviral drugs currently on the market act as neuraminidase inhibitors (zanamivir, oseltamivir, peramivir) or target the M2-ion channel (amantadine, rimantadine); however, due to the lack of viral proof-reading enzymes, these targets are prone to rapid mutations that often confer antiviral resistance. In contrast, the viral RNA-dependent RNA polymerase (RdRp) is an attractive drug target because it is relatively slow to develop drug resistance, conserved across genotypes, and essential to viral replication. With no eukaryotic homologue, the potential for toxicity due to off-target effects is low for RdRp targeting compounds. Our research focuses on targeting the endonuclease domain of the RdRp, located on the PA N-terminal domain, which has a two metal binding active site. We have developed a series of 2-substituted dihydroxypyrimidine carboxamides which bind to the endonuclease active site and disrupt its activity in vitro. The activity of these compounds has been validated by fluorescent polarization binding assays and plaque inhibition assays. The most potent inhibitors have been co-crystallized with PAN to determine the structure-activity relationships, allowing us to improve their efficacy. We will discuss the structure-activity relationship of our analogs and several interesting protein-small molecule X-ray crystal structures, as well as our progress on the development of an innovative therapeutic lead compound targeting influenza endonuclease.

Speaker
Biography:

Gyanendra Kumar has earned his PhD from IISc, Bangalore in 2007 and then joined the Brookhaven National Laboratory, New York and worked on drug discovery for Botulinum neurotoxins. Currently, he is a Postdoctoral Research Associate at the Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, working on the drug discovery for influenza by targeting the endonuclease domain of viral RdRp. He has published numerous research articles on malaria, botulism and influenza and presented his work at international conferences. He serves as a Referee for several journals and is a Member of ACS, ACA, AAAS and ISIRV.

Abstract:

The influenza endonuclease is an essential sub-domain of the viral RNA polymerase. It processes host pre-mRNAs to serve as primers for viral mRNA and is an attractive target for anti-influenza drug discovery. Compound L-742,001 is a prototypical endonuclease inhibitor, and we found that repeated passaging of influenza virus in the presence of this inhibitor did not lead to the development of resistant mutant strains. Reduced sensitivity to L-742,001 could only be induced by creating point mutations via a random mutagenesis strategy. These mutations mapped to the endonuclease active site where they can directly impact inhibitor binding. Engineered viruses containing the mutations showed resistance to L-742,001 both in vitro and in vivo, with only a modest reduction in fitness. Introduction of the mutations into a second virus also increased its resistance to the inhibitor. Using the isolated wild-type and mutant endonuclease domains, we used kinetics, inhibitor binding and crystallography to characterize how the two most significant mutations elicit resistance to L-742,001. These studies lay the foundation for the development of a new class of influenza therapeutics with reduced potential for the development of clinical endonuclease inhibitor resistant influenza strains.

Periolo Natalia

INEI-ANLIS "Carlos G. Malbran", Argentina

Title: Pregnancy and severity of infection with pandemic influenza A(H1N1)pdm09virus

Time : 13:45-14:10

Speaker
Biography:

Periolo Natalia has completed his PhD at the age of 31 years from Quilmes University, buenos Aires, Argentina.She had a International Fellowship postdoctoral from the Department of Immunology, The Wenner-Gren Institute, Stockholm University. Actually, she is researcher of The National Scientific and Technical Research Council (CONICET) and work at the Institute INEI-ANLIS "Carlos G. Malbran", Argentina. She has published more than 10 papers in reputed journals.

Abstract:

Pregnant women are at increased risk for severe illness from influenza virus infection. Immunological and hormonal alterations place women at increased riskfor influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09infection resulted in increased disease severity in pregnant women, the precise mechanisms responsiblefor this risk have yet to be established. During the 2009 H1N1 influenza A pandemic, pregnant women were generally at increased risk for severe disease, including disease leading to hospitalization, admission to an intensive care unit, or death, as compared with nonpregnant women and the general population. In Argentina, it was estimated that the mortality rate per 100,000 person-years (py) ranged from 1.5 among persons aged 5–44 years to 5.6 among persons aged ≥65 years. An analysis of 332 case fatalities infectedwith A(H1N1)pdm09 virus showed that twenty (6%) were among pregnant or postpartum women of who monly 47% had been diag-nosed with comorbid disorders .Studies have demonstrated that the over-production of specific inflammatory cytokines, such as the tumor necrosis factor (TNF)-,interleukin (IL), IL-6 and IL-10, as well as the polymorphonuclearneutrophil CC chemokine- IL-8, is the hallmark of viral infection. In an attempt to elucidate the innate immune response to A(H1N1) pdm09 infection and to gain further insight into cytokine-mediated pathogenesis, we retrospectively evaluated the expression levels of a panel of cytokines, chemokines, and viral replication in different groups of pregnant women according to the severity of the infection.

Speaker
Biography:

Jennifer M Reiman is an Immunologist with expertise in infectious diseases and cancer. She is interested in reducing the spread of infectious diseases such as respiratory viruses, particularly influenza. Her research is aimed at finding easy and cost-effective interventions to reduce respiratory virus transmission including the possibility of humidification during dry (low humidity) winter conditions in temperate climates such as Minnesota, USA. She is also involved in science education partnerships with schools (pre-K through middle school) through Integrated Science Education Outreach (InSciEd Out) a non-profit based within the Center for Clinical and Translational Science and Department of Biochemistry and Molecular Biology at the Mayo Clinic in Rochester, MN.

Abstract:

Statement of the Problem: Annual influenza epidemics are responsible for 250000- 500000 deaths worldwide. Preschool and elementary school classrooms represent a significant source of influenza. There is a need for cost effective interventions that reduce influenza and respiratory illnesses in classrooms.

Methodology: Study was conducted at Aldrich Memorial Nursery School, Rochester, MN (a preschool with students aged 2-5 years) from January 2016-March 2016. Classrooms of identical design each with their own HVAC system for air handling were utilized. Two classrooms had humidifiers (DriSteem) installed and were compared to two non-humidified classrooms (control rooms) with similar aged students. Data on outdoor and classroom temperatures and relative humidity was gathered to calculate absolute humidity. Air samples were collected using NIOSH samplers. Fomites were collected from objects (e.g., markers, wooden blocks) wrapped in 25% cotton linen paper that students interacted with. Paper and air samples were further processed to determine infectivity (in cell culture) or viral RNA presence and quantity by qRT-PCR.

Conclusion & Significance: Absolute humidity from January 25-March 11, 2016 for outdoors as well as indoor classroom environments is depicted. With humidification we were able to maintain elevated absolute humidity at an average of 9.89 mb compared to 6.33 mb in control rooms (1/25/16-2/23/16). Humidifiers were turned off after sample collection on 2/23/16 as ambient humidity had increased in control rooms approaching that of humidified rooms. Additionally, we investigated if there were differences in the amount of influenza A RNA in positive samples. We quantitated the NS1 gene copy number and compared samples to our standard curve with known copy numbers of the gene. The median copy number between the two groups (humidified versus controls) was statistically significant for both paper (P= 0.043, t=2.123) and air (P=0.032, t=2.435).

Speaker
Biography:

Andrew C.Y. Lee is a PhD candidate in the Department of Microbiology, The University of Hong Kong. My research focuses on the pathogenesis of avian influenza A H7N9 virus.

Abstract:

Following the 2013 outbreak of human infection with avian influenza A H7N9 virus, sporadic human infections have continued to occur in China. To better understand the mechanisms as how H7N9 virus causes severe illness in human, we infected human PBMCs with H7N9 (A/Anhui/1/2013) and compared to H5N1 (A/VNM/1194/2004) and 2009 pandemic H1N1 (A/HK/415742/2009) viruses. We found that H7N9 virus was as infectious as H5N1 virus to PBMCs, with large proportion of cells expressing viral antigen at 12 hours after inoculation with 2 M.O.I of each viruses, while pH1N1 infected much less of cells. Moreover, our results showed that H7N9 induced cytokine responses that were similar to that of H5N1, but different from that of pH1N1. Result of multi-color flow cytometry indicated that all three viruses were able to infect multiple cell types including CD14+ monocytes, CD4+ T cells, CD8+ T cells and CD19+ B cells. Among different cell types, CD14+ monocytes were highly susceptible to both H7N9 and H5N1 infection but less susceptible to pH1N1 infection. Surprisingly, we found that H7N9 and H5N1 virus infection caused CD14+ monocytes quickly disappeared from the PBMC culture within 12 hours. Further study of purified the CD14+ monocytes showed that both H7N9 and H5N1 caused rapid down regulation of cell surface CD14 molecules, induced massive activation of caspase 3. TNEUL assay indicated that H7N9 and H5N1 induced apoptotic cell death in monocytes. Overall, these results suggested H7N9 virus is highly infective to human immune cells; infection of PBMCs provoked similar profile of cytokine responses and massive apoptosis of monocytes as seen in highly pathogenic H5N1 virus infection. H7N9 and H5N1 may share similar pathogenic mechanisms to cause severe disease in humans.

Speaker
Biography:

Zhu Houshun is the PhD student in the department of Medicine of the University of Hong Kong. His research mainly focuses on the treatment of influenza infection.

Abstract:

Mouse beta-Defesin 4(mBD4) is mainly produced by epithelial cells and should play an important role during influenza infection. Firstly, we showed that mBD4 was quickly increased in LA4 cells at 6 hours after inoculation with A(H1N1)09 virus and remained upregulated until 24 hours post infection. The induction of mBD4 was positively correlated with initial virus inoculation doses.The time course for the induction of mBD4 was in parallel with the upregualtion of inflammatory cytokine IL-6 and TNF-α. The expresssion of mBD4 in mouse respiratory tissue was studied and compared between young(6-8 weeks) and aged (72 weeks) mice. IHC staining of formalin fixed mice trachea and lung tissues showed there was stronger expression of mBD4 in epithelial cells lining trachea and broncheoles in aged mice which indicated a higher basal expression of mBD4 in aged mice respiratory tissues. Upon infection with A(H1N1)09 virus, a quick induction of mBD4 in young mice trachea tissue was observed at 12h p.i. and maintained at this level until day 4 p.i.. However, despite the higher basal level, there was no further induction of mBD4 in aged mice trachea tissues. For the lung tissues, delayed induction of mBD4 was observed in aged mice following A(H1N1)09 infection, but no increase was observed in the young mice lung tissues. Accordingly we also see a lower viral load and cytokine levels in young mice. After giving the recombinant mBD4 protein after infection of A(H1N1)09 in aged mice, we saw a reduced viral load in respiratory tissues.

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