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Lessons learned from Asian H5N1 outbreak control

Sims LD

Avian Dis, 2007 Mar;51(1 Suppl):174-81.
PMID: 17494550

Numerous lessons have been learned so far in controlling H5N1 avian influenza in Asia. Early detection of incursions of virus prevented establishment of the disease in several countries, notably Japan, South Korea, and Malaysia. In countries where detection of early cases was delayed, infection is endemic and has been for three or more years. Control measures implemented in these countries need to reflect this finding. Vaccination will continue to be one of the key measures used in these endemically infected countries. Used alone, vaccination will not result in elimination of H5N1 viruses from a country, but, if used correctly, it will markedly reduce the prevalence of and susceptibility to infection. Vaccination has already played a valuable role in reducing the adverse effects of H5N1 viruses. Mass culling also reduces the level of infection in infected areas. However, the long-term benefits are limited in endemically infected countries owing to the high probability of reinfection on restocking unless other measures are used in parallel. Full epidemiological studies have not been conducted in many infected countries. Nevertheless, it is recognized that the number of clinical cases does not truly reflect the levels of infection. Domestic ducks and large live poultry markets have played a key role in the persistence of infection, because they can be infected silently. In tackling this disease, countries should adopt integrated control programs using the combination of measures best suited to the local environment. All surveillance data should be shared, both positive and negative, and should include information on cases of infection and disease. Socioeconomic and ecological implications of all control measures should be assessed before implementation, especially the impact on the rural poor.

Matched MeSH terms: Influenza A Virus, H5N1 Subtype/isolation & purification; Influenza A Virus, H5N1 Subtype/physiology*
Fulltext Construction and heterologous expression of a truncated Haemagglutinin (HA) protein from the avian influenza virus H5N1 in Escherichia coli

Chee Wei T, Nurul Wahida AG, Shaharum S

Trop Biomed, 2014 Dec;31(4):792-801.
PMID: 25776606 MyJurnal

Malaysia first reported H5N1 poultry case in 2004 and subsequently outbreak in poultry population in 2007. Here, a recombinant gene encoding of peptide epitopes, consisting fragments of HA1, HA2 and a polybasic cleavage site of H5N1 strain Malaysia, was amplified and cloned into pET-47b(+) bacterial expression vector. DNA sequencing and alignment analysis confirmed that the gene had no alteration and in-frame to the vector. Then, His-tagged truncated HA protein was expressed in Escherichia coli BL21 (DE3) under 1 mM IPTG induction. The protein expression was optimized under a time-course induction study and further purified using Ni-NTA agarose under reducing condition. Migration size of protein was detected at 15 kDa by Western blot using anti-His tag monoclonal antibody and demonstrated no discrepancy compared to its calculated molecular weight.

Matched MeSH terms: Influenza A Virus, H5N1 Subtype/genetics*; Influenza A Virus, H5N1 Subtype/isolation & purification
H274Y's Effect on Oseltamivir Resistance: What Happens Before the Drug Enters the Binding Site

Yusuf M, Mohamed N, Mohamad S, Janezic D, Damodaran KV, Wahab HA

J Chem Inf Model, 2016 Jan 25;56(1):82-100.
PMID: 26703840 DOI: 10.1021/acs.jcim.5b00331

Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug.

Matched MeSH terms: Influenza A Virus, H5N1 Subtype/drug effects; Influenza A Virus, H5N1 Subtype/enzymology
Seasonal influenza activity based on laboratory surveillance in Malaysia, 2011-2016

Sam IC, Noraini W, Sandhu SS, Norizah I, Selvanesan S, Thayan R, et al.

J Med Virol, 2019 03;91(3):498-502.
PMID: 30199092 DOI: 10.1002/jmv.25313

Influenza seasonality in equatorial countries is little understood. Seasonal and alert influenza thresholds were determined for Malaysia, using laboratory-based data obtained from the Malaysia Influenza Surveillance System and a major teaching hospital, from 2011 to 2016. Influenza was present year-round, with no clear annual seasons. Variable periods of higher transmission occurred inconsistently, in November to December, January to March, July to September, or a combination of these. These coincide with seasons in the nearby southeast Asian countries or winter seasons of the northern and southern hemispheres. Changes in the predominant circulating influenza type were only sometimes associated with increased transmission. The data can provide public health interventions such as vaccines.

Matched MeSH terms: Influenza A virus
Fulltext Universal oral vaccine for influenza infections

Yap, Wei Boon, Toong, Seng Tan, Sharifah Syed Hassan, Jeffrey Cheah

Jurnal Sains Kesihatan Malaysia, 2018;16(2):51-64.
MyJurnal

Each year, influenza A infections have caused tremendous death rate as high as 300,000-500,000 globally. Although
there are effective anti-influenza agents and vaccines, high mutational rate among influenza A viruses renders dramatic
decline in the effectiveness of anti-influenza agents or vaccines in certain individuals. The situation is further complicated
by limitations in influenza vaccine production, for instance, long production period, limited vaccine capacity and lack
of cross-protection against various influenza A virus strains. To solve these issues, development of universal influenza
vaccine based on conserved antigens such as non-stuctural protein 1 (NS1) has been endeavoured. NS1 protein is highly
conserved in all influenza A virus strains known by far, produced abundantly on infected cell surfaces and responsible for
maintaining virulence. Furthermore, cytotoxic T-lymphocytes that are active against NS1 were also reported to be able
to avoid shedding of influenza in hosts. To better inhibit influenza infections, oral immunization has long been proposed
due to feasibility of this method to be implemented and safer for recipients while able to target influenza A viruses from
the entry point. Lactobacillus has been vastly studied for its roles as bacterial carrier in oral vaccine development due
to its significant probiotic properties. For examples, stimulation of immune responses in oral and airway mucosal layers,
high colonization in oral and airway mucosal layers and great natural adjuvant effects. In this light, influenza universal
oral vaccine developed using NS1 dan Lactobacillus should be further studied in influenza oral vaccine design.

Matched MeSH terms: Influenza A virus
Assessment of efficacy of Oseltamivir-Azithromycin combination therapy in prevention of Influenza-A (H1N1)pdm09 infection complications and rapidity of symptoms relief

Ishaqui AA, Khan AH, Sulaiman SAS, Alsultan MT, Khan I, Naqvi AA

Expert Rev Respir Med, 2020 05;14(5):533-541.
PMID: 32053044 DOI: 10.1080/17476348.2020.1730180

Objectives: This study aimed to assess the efficacy of oseltamivir-Azithromycin combination therapy for prevention of Influenza-A (H1N1)pdm09 infection associated complications and early relief of influenza symptoms.Methods: In a retrospective observational cohort study, Influenza-A (H1N1)pdm09 infection hospitalized patients were identified and divided into two groups based on the initial therapy. Group-AV patients were initiated on Oseltamivir without any antibiotic in treatment regimen while Group-AV+AZ patients were initiated on Oseltamivir and Azithromycin combination therapy for at least 3-5 days. Patients were evaluated for different clinical outcomes.Results: A total of 227 and 102 patients were identified for Group-AV and Group-AV+AZ respectively. Multivariate regression analysis showed that incidences of secondary bacterial infections were significantly less frequent (23.4% vs 10.4%; P-value = 0.019) in Group-AV+AZ patients. Group-AV+AZ patients were associated with shorter length of hospitalization (6.58 vs 5.09 days; P-value = <0.0001) and less frequent incidences of respiratory support (38.3% vs 17.6%; P-value = 0.016). Overall influenza symptom severity score was statistically significant less for Group-AV+AZ patients on Day-5 (10.68 ± 2.09; P-value = 0.001) of hospitalization.Conclusion: Oseltamivir-Azithromycin combination therapy was found to be more efficacious as compared to oseltamivir alone in rapid recovery and prevention of Influenza associated complications especially in high risk patients.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype
Insertion of single-chain variable fragment (scFv) peptide linker improves surface display of influenza hemagglutinin (HA1) on non-recombinant Lactococcus lactis

Jee PF, Chen FS, Shu MH, Wong WF, Abdul Rahim R, AbuBakar S, et al.

Biotechnol Prog, 2017 Jan;33(1):154-162.
PMID: 27802566 DOI: 10.1002/btpr.2400

Heterologous protein displayed on the surface of Lactococcus lactis using the binding domain of N-acetylmuramidase (AcmA) has a potential application in vaccine delivery. In this study, we developed a non-recombinant L. lactis surface displaying the influenza A (H1N1) 2009 hemagglutinin (HA1). Three recombinant proteins, HA1/L/AcmA, HA1/AcmA, and HA1 were overexpressed in Escherichia coli, and purified. In the binding study using flow cytometry, the HA1/L/AcmA, which contained the single-chain variable fragment (scFv) peptide linker showed significantly higher percentage of binding counts and mean fluorescence binding intensity (MFI) (51.7 ± 1.4% and 3,594.0 ± 675.9, respectively) in comparison to the HA1/AcmA without the scFv peptide linker (41.1 ± 1.5% and 1,652.0 ± 34.1, respectively). Higher amount of HA1/L/AcmA (∼2.9 × 10(4) molecules per cell) was displayed on L. lactis when compared to HA1/AcmA (∼1.1 × 10(4) molecules per cell) in the immunoblotting analysis. The HA1/L/AcmA completely agglutinated RBCs at comparable amount of protein to that of HA1/AcmA and HA1. Computational modeling of protein structures suggested that scFv peptide linker in HA1/L/AcmA kept the HA1 and the AcmA domain separated at a much longer distance in comparison to HA1/AcmA. These findings suggest that insertion of the scFv peptide linker between HA1 and AcmA improved binding of recombinant proteins to L. lactis. Hence, insertion of scFv peptide linker can be further investigated as a potential approach for improvement of heterologous proteins displayed on the surface of L. lactis using the AcmA binding domain. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:154-162, 2017.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype
Fulltext Tracking the source and origin of H5N1 avian influenza viruses in Malaysia

Sharifah, S .H., Suriani, M. N., Hassuzana, K., Aini, I.

Buletin Persatuan Genetik Malaysia, 2006;12(1):1-3.
MyJurnal

Malaysia, experienced two epidemic waves of HPAI; its fi rst outbreak of HP H5N1 in August 2004 that occurred in the state of Kelantan and the second and subsequent outbreaks in February–March 2006 in three states on the west coast of Malaysia namely Wilayah Persekutuan
Kuala Lumpur, Perak and Penang. Five outbreaks occurred in village chickens and one in a multi-species enclosure of birds in a bird park resort facility. Molecular epidemiological studies by genomic sequencing and phylogenetic analyses of the viruses isolated showed that the
virus isolated from WP Kuala Lumpur is of the V-genotype and it originated from Hunan China, two viruses were found to be similar to the Fujian/Hunan strains and other viruses were similar to the Vietnam/ Thailand strains.

Matched MeSH terms: Influenza A Virus, H5N1 Subtype
Fulltext Community awareness and attitudes towards influenza outbreak and prevention in Serian, Sarawak

Rohaya Mohd-Nor, Rose Nanju@Manju, Samuel Lihan, Sidiah John Siop, Rekaya Vincent Balang, Constance Rinen Justin Wah, et al.

Int J Public Health Res, 2013;3(2):334-346.
MyJurnal

To date, there has been no systematic research that investigates the rural community awareness and attitudes towards pandemic influenza H1N1 and its prevention measures in the context of Sarawak. There is also no systematic study about whether the initiatives to educate the public undertaken by the government and other agencies have empowered the rural communities to practice an effective self-care within the context of community, that assist to curb the potential spread of this disease. Our research aims to address these limitations. In this paper, we report a survey finding about the awareness and attitudes of the Serian community with regard to this area of research interest. We also investigate the relevant sources of information that the community relies on in understanding about the influenza and how it can spread. Overall, the outcomes of the survey reveal that a majority of our respondents has a relatively low level of knowledge and awareness particularly about the characteristics of the illness and how H1N1 virus can transmit. With regard to prevention measures, a majority of them reported good understanding and awareness about the effective self-care practices that can help to curb the potential spread of the influenza. The top five sources to obtain information about the influenza were: information from family, relatives, friends or neighbours; radio; TV; newspapers; and government health talk seminar or campaigns. The research outcomes can offer pragmatic contributions that can benefit the health campaigners and policy makers.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype
Fulltext Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound

Muchtaridi M, Lestari D, Khairul Ikram NK, Gazzali AM, Hariono M, Wahab HA

Molecules, 2021 Jun 04;26(11).
PMID: 34199752 DOI: 10.3390/molecules26113402

Coffee has been studied for its health benefits, including prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson's, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. However, the presence of caffeine in coffee beans may also cause insomnia and stomach irritation, and increase heart rate and respiration rate. These unwanted effects may be reduced by decaffeination of green bean Arabica coffee (GBAC) by treatment with dichloromethane, followed by solid-phase extraction using methanol. In this study, the caffeine and chlorogenic acid (CGA) level in the coffee bean from three different areas in West Java, before and after decaffeination, was determined and validated using HPLC. The results showed that the levels of caffeine were reduced significantly, with an order as follows: Tasikmalaya (2.28% to 0.097% (97 ppm), Pangalengan (1.57% to 0.049% (495 ppm), and Garut (1.45% to 0.00002% (0.2 ppm). The CGA levels in the GBAC were also reduced as follows: Tasikmalaya (0.54% to 0.001% (118 ppm), Pangalengan (0.97% to 0.0047% (388 ppm)), and Garut (0.81% to 0.029% (282 ppm). The decaffeinated samples were then subjected to the H5N1 neuraminidase (NA) binding assay to determine its bioactivity as an anti-influenza agent. The results show that samples from Tasikmalaya, Pangalengan, and Garut possess NA inhibitory activity with IC50 of 69.70, 75.23, and 55.74 μg/mL, respectively. The low level of caffeine with a higher level of CGA correlates with their higher levels of NA inhibitory, as shown in the Garut samples. Therefore, the level of caffeine and CGA influenced the level of NA inhibitory activity. This is supported by the validation of CGA-NA binding interaction via molecular docking and pharmacophore modeling; hence, CGA could potentially serve as a bioactive compound for neuraminidase activity in GBAC.

Matched MeSH terms: Influenza A Virus, H5N1 Subtype/drug effects; Influenza A Virus, H5N1 Subtype/enzymology*; Influenza A Virus, H5N1 Subtype/chemistry
Silver linings: a qualitative study of desirable changes to cancer care during the COVID-19 pandemic

Lombe D, Sullivan R, Caduff C, Ali Z, Bhoo-Pathy N, Cleary J, et al.

Ecancermedicalscience, 2021;15:1202.
PMID: 33889211 DOI: 10.3332/ecancer.2021.1202

Introduction: Public health emergencies and crises such as the current COVID-19 pandemic can accelerate innovation and place renewed focus on the value of health interventions. Capturing important lessons learnt, both positive and negative, is vital. We aimed to document the perceived positive changes (silver linings) in cancer care that emerged during the COVID-19 pandemic and identify challenges that may limit their long-term adoption.
Methods: This study employed a qualitative design. Semi-structured interviews (n = 20) were conducted with key opinion leaders from 14 countries. The participants were predominantly members of the International COVID-19 and Cancer Taskforce, who convened in March 2020 to address delivery of cancer care in the context of the pandemic. The Framework Method was employed to analyse the positive changes of the pandemic with corresponding challenges to their maintenance post-pandemic.
Results: Ten themes of positive changes were identified which included: value in cancer care, digital communication, convenience, inclusivity and cooperation, decentralisation of cancer care, acceleration of policy change, human interactions, hygiene practices, health awareness and promotion and systems improvement. Impediments to the scale-up of these positive changes included resource disparities and variation in legal frameworks across regions. Barriers were largely attributed to behaviours and attitudes of stakeholders.
Conclusion: The COVID-19 pandemic has led to important value-based innovations and changes for better cancer care across different health systems. The challenges to maintaining/implementing these changes vary by setting. Efforts are needed to implement improved elements of care that evolved during the pandemic.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype
Evaluation of the safety, reactogenicity and immunogenicity of FluBlok® trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age

Baxter R, Patriarca PA, Ensor K, Izikson R, Goldenthal KL, Cox MM

Vaccine, 2011 Mar 9;29(12):2272-8.
PMID: 21277410 DOI: 10.1016/j.vaccine.2011.01.039

Alternative methods for influenza vaccine production are needed to ensure adequate supplies.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/immunology; Influenza A Virus, H3N2 Subtype/immunology
Immunogenicity and tolerability of a virosome influenza vaccine compared to split influenza vaccine in patients with sickle cell anemia

Souza AR, Braga JA, de Paiva TM, Loggetto SR, Azevedo RS, Weckx LY

Vaccine, 2010 Jan 22;28(4):1117-20.
PMID: 20116631 DOI: 10.1016/j.vaccine.2009.05.046

The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated. Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n=43) or split vaccine (n=47). Two blood samples were collected, one before and one 4-6 weeks after vaccination. Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test. Post-vaccine reactions were recorded over 7 days. Seroconversion rates for H1N1, H3N2 and B were 65.1%, 60.4% and 83.7% for virosome vaccine, and 68.0%, 61.7% and 68.0% for split vaccine. Seroprotection rates for H1N1, H3N2 e B were 100%, 97.6% and 69.7% for virosome, and 97.8%, 97.8% and 76.6% for split vaccine. No severe adverse reactions were recorded. Virosome and split vaccines in patients with sickle cell anemia were equally immunogenic, with high seroconversion and seroprotection rates. Both vaccines were well tolerated.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/immunology; Influenza A Virus, H3N2 Subtype/immunology
Avian Influenza Virus and DIVA Strategies

Hasan NH, Ignjatovic J, Peaston A, Hemmatzadeh F

Viral Immunol, 2016 05;29(4):198-211.
PMID: 26900835 DOI: 10.1089/vim.2015.0127

Vaccination is becoming a more acceptable option in the effort to eradicate avian influenza viruses (AIV) from commercial poultry, especially in countries where AIV is endemic. The main concern surrounding this option has been the inability of the conventional serological tests to differentiate antibodies produced due to vaccination from antibodies produced in response to virus infection. In attempts to address this issue, at least six strategies have been formulated, aiming to differentiate infected from vaccinated animals (DIVA), namely (i) sentinel birds, (ii) subunit vaccine, (iii) heterologous neuraminidase (NA), (iv) nonstructural 1 (NS1) protein, (v) matrix 2 ectodomain (M2e) protein, and (vi) haemagglutinin subunit 2 (HA2) glycoprotein. This short review briefly discusses the strengths and limitations of these DIVA strategies, together with the feasibility and practicality of the options as a part of the surveillance program directed toward the eventual eradication of AIV from poultry in countries where highly pathogenic avian influenza is endemic.

Matched MeSH terms: Influenza A virus/immunology*; Influenza A virus/isolation & purification; Influenza A virus/pathogenicity
Fulltext The burden of human influenza in Malaysia

Sam JIC

Med J Malaysia, 2015 Jun;70(3):127-30.
PMID: 26248773 MyJurnal

Seasonal and pandemic influenza causes considerable morbidity and mortality globally, but the burden of disease is understudied and underreported in developing countries such as Malaysia. Before considering the cost-effectiveness of introducing interventions such as vaccines to control influenza, it is imperative to determine clinical and socioeconomic impact of the disease. This review summarises the main available literature on human influenza in Malaysia, the possible reasons for the lack of study and awareness of influenza, and important knowledge gaps for future study.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype
Prevalence of avian influenza (H9N2) in commercial quail, partridge, and turkey farms in Iran, 2014-2015

Mehrabadi MHF, Bahonar A, Mirzaei K, Molouki A, Ghalyanchilangeroudi A, Ghafouri SA, et al.

Trop Anim Health Prod, 2018 Mar;50(3):677-682.
PMID: 29027604 DOI: 10.1007/s11250-017-1438-x

Avian influenza virus (AIV) H9N2 subtype is endemic in Iran and causes substantial economic loss to the growing poultry industry within the country. In this study, a cross-sectional analysis was carried out to determine the sero-prevalence of H9N2 in several commercial farms between the years 2014 and 2015. The comparison of the mean of serum titers and the ratio of sero-positive birds between all units were analyzed using one-way ANOVA test. In 2014, a total of 77 farms (58 turkey farms, 14 quail farms, and 5 partridge farms) and 894 birds (682 turkeys, 154 quails, and 58 partridges) were sampled while in 2015, a total of 69 farms (54 turkey farms, 8 quail farms, and 7 partridge farms) and 856 birds (675 turkeys, 105 quails, and 76 partridges) were sampled. Of that, 52 of 77 sampled farms (67.5%) and 437 of 894 samples (48.9%) were positive for H9N2 in 2014 while. Forty-one of 69 farms (59.4%) and 307 of 856 sera (35.9%) were positive in 2015. Furthermore, the mean titer of partridge farms was significantly lower than that of turkey farms (p 0.05). Our results indicated that H9N2 is circulating in these farms. Since many more such farms are being established for operations, in addition to the threat of emergence and continuous reemergence of the disease in these farms, enhanced veterinary biosecurity measures on farms are required for mitigation.

Matched MeSH terms: Influenza A Virus, H9N2 Subtype*
Influenza A virus neuraminidase protein interacts with Hsp90, to stabilize itself and enhance cell survival

Kumar P, Gaur P, Kumari R, Lal SK

J Cell Biochem, 2019 04;120(4):6449-6458.
PMID: 30335904 DOI: 10.1002/jcb.27935

Neuraminidase protein (NA) of influenza A virus (IAV) is popularly known for its sialidase function to assist in the release of progeny virus. However, involvement of NA in other stages of the IAV life cycle also indicates its multifunctional nature and necessity to interact with other host proteins. Here, we report a host protein-heat shock protein 90 (Hsp90), as a novel interacting partner of IAV NA. A classical yeast two-hybrid screen was conducted to identify a new host interacting partner for NA and the interaction was further validated by coimmunoprecipitation from cells, transiently expressing both proteins and also from IAV-infected cells. Confocal imaging showed that both proteins colocalized in the cytoplasm in transfected host cells. Interestingly, increased levels of NA in the presence of Hsp90 was observed, which tends to decrease if adenosine triphosphatase activity of Hsp90 is inhibited using 17-N-allylamino-17-demethoxygeldanamycin (17AAG). This establishes viral NA as a client protein of host chaperone Hsp90 contributing toward NA's stability via the NA-Hsp90 interaction. This is the first report showing the interaction of NA with Hsp90 and its role in stabilizing viral NA thus preventing it from degradation. Enhanced cell survival in the presence of this interaction was also observed, thus suggesting the requirement of stable viral NA, post-IAV infection, for efficient virus production in infected mammalian cells.

Matched MeSH terms: Influenza A virus/physiology*
Fulltext Interferon Regulatory Factors IRF1 and IRF7 Directly Regulate Gene Expression in Bats in Response to Viral Infection

Irving AT, Zhang Q, Kong PS, Luko K, Rozario P, Wen M, et al.

Cell Rep, 2020 11 03;33(5):108345.
PMID: 33147460 DOI: 10.1016/j.celrep.2020.108345

Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.

Matched MeSH terms: Influenza A virus/immunology
QSAR model for predicting neuraminidase inhibitors of influenza A viruses (H1N1) based on adaptive grasshopper optimization algorithm

Algamal ZY, Qasim MK, Lee MH, Ali HTM

SAR QSAR Environ Res, 2020 Nov;31(11):803-814.
PMID: 32938208 DOI: 10.1080/1062936X.2020.1818616

High-dimensionality is one of the major problems which affect the quality of the quantitative structure-activity relationship (QSAR) modelling. Obtaining a reliable QSAR model with few descriptors is an essential procedure in chemometrics. The binary grasshopper optimization algorithm (BGOA) is a new meta-heuristic optimization algorithm, which has been used successfully to perform feature selection. In this paper, four new transfer functions were adapted to improve the exploration and exploitation capability of the BGOA in QSAR modelling of influenza A viruses (H1N1). The QSAR model with these new quadratic transfer functions was internally and externally validated based on MSEtrain, Y-randomization test, MSEtest, and the applicability domain (AD). The validation results indicate that the model is robust and not due to chance correlation. In addition, the results indicate that the descriptor selection and prediction performance of the QSAR model for training dataset outperform the other S-shaped and V-shaped transfer functions. QSAR model using quadratic transfer function shows the lowest MSEtrain. For the test dataset, proposed QSAR model shows lower value of MSEtest compared with the other methods, indicating its higher predictive ability. In conclusion, the results reveal that the proposed QSAR model is an efficient approach for modelling high-dimensional QSAR models and it is useful for the estimation of IC50 values of neuraminidase inhibitors that have not been experimentally tested.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/enzymology*
A case-control study of influenza vaccine effectiveness among Malaysian pilgrims attending the Haj in Saudi Arabia

Mustafa AN, Gessner BD, Ismail R, Yusoff AF, Abdullah N, Ishak I, et al.

Int J Infect Dis, 2003 Sep;7(3):210-4.
PMID: 14563225

To determine influenza vaccine effectiveness against clinically defined influenza-like illness among Malaysian pilgrims attending the Haj in Saudi Arabia.

Matched MeSH terms: Influenza A virus/immunology

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