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The survival of influenza A(H1N1)pdm09 virus on 4 household surfaces

Oxford J, Berezin EN, Courvalin P, Dwyer DE, Exner M, Jana LA, et al.

Am J Infect Control, 2014 Apr;42(4):423-5.
PMID: 24679569 DOI: 10.1016/j.ajic.2013.10.016

We investigated the survival of a pandemic strain of influenza A H1N1 on a variety of common household surfaces where multiple samples were taken from 4 types of common household fomite at 7 time points. Results showed that influenza A H1N1sw virus particles remained infectious for 48 hours on a wooden surface, for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth surface, although virus recovery from the cloth may have been suboptimal. Our results suggest that pandemic influenza A H1N1 can survive on common household fomites for extended periods of time, and that good hand hygiene and regular disinfection of commonly touched surfaces should be practiced during the influenza season to help reduce transmission.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/physiology*
Fulltext Characteristics of children hospitalized for pandemic (H1N1) 2009, Malaysia

Muhammad Ismail HI, Tan KK, Lee YL, Pau WS, Razali KA, Mohamed T, et al.

Emerg Infect Dis, 2011 Apr;17(4):708-10.
PMID: 21470467 DOI: 10.3201/eid1704.101212

To determine effects of pandemic (H1N1) 2009 on children in the tropics, we examined characteristics of children hospitalized for this disease in Malaysia. Of 1,362 children, 51 (3.7%) died, 46 of whom were in an intensive care unit. Although disease was usually mild, ≥ 1 concurrent conditions were associated with higher death rates.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/physiology*
Fulltext Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells

Hussain AI, Cordeiro M, Sevilla E, Liu J

Vaccine, 2010 May 14;28(22):3848-55.
PMID: 20307595 DOI: 10.1016/j.vaccine.2010.03.005

Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/physiology
Fulltext Edible bird's nest modulate intracellular molecular pathways of influenza A virus infected cells

Haghani A, Mehrbod P, Safi N, Kadir FA, Omar AR, Ideris A

BMC Complement Altern Med, 2017 Jan 05;17(1):22.
PMID: 28056926 DOI: 10.1186/s12906-016-1498-x

BACKGROUND: Edible Bird's Nest (EBN) as a popular traditional Chinese medicine is believed to have health enhancing and antiviral activities against influenza A virus (IAV); however, the molecular mechanism behind therapeutic effects of EBN is not well characterized.
METHODS: In this study, EBNs that underwent different enzymatic preparation were tested against IAV infected cells. 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50) of the EBNs against IAV strain A/Puerto Rico/8/1934(H1N1) were determined by HA and MTT assays. Subsequently, the sialic acid content of the used EBNs were analyzed by fluorometric HPLC. Western Blotting and immunofluorescent staining were used to investigate the effects of EBNs on early endosomal trafficking and autophagy process of influenza virus.
RESULTS: This study showed that post inoculations of EBNs after enzymatic preparations have the highest efficacy to inhibit IAV. While CC50 of the tested EBNs ranged from 27.5-32 mg/ml, the IC50 of these compounds ranged between 2.5-4.9 mg/ml. EBNs could inhibit IAV as efficient as commercial antiviral agents, such as amantadine and oseltamivir with different mechanisms of action against IAV. The antiviral activity of these EBNs correlated with the content of N-acetyl neuraminic acid. EBNs could affect early endosomal trafficking of the virus by reducing Rab5 and RhoA GTPase proteins and also reoriented actin cytoskeleton of IAV infected cells. In addition, for the first time this study showed that EBNs can inhibit intracellular autophagy process of IAV life cycle as evidenced by reduction of LC3-II and increasing of lysosomal degradation.
CONCLUSIONS: The results procured in this study support the potential of EBNs as supplementary medication or alternative to antiviral agents to inhibit influenza infections. Evidently, EBNs can be a promising antiviral agent; however, these natural compounds should be screened for their metabolites prior to usage as therapeutic approach.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/physiology
Structurally conserved binding sites of hemagglutinin as targets for influenza drug and vaccine development

Yusuf M, Konc J, Sy Bing C, Trykowska Konc J, Ahmad Khairudin NB, Janezic D, et al.

J Chem Inf Model, 2013 Sep 23;53(9):2423-36.
PMID: 23980878 DOI: 10.1021/ci400421e

ProBiS is a new method to identify the binding site of protein through local structural alignment against the nonredundant Protein Data Bank (PDB), which may result in unique findings compared to the energy-based, geometry-based, and sequence-based predictors. In this work, binding sites of Hemagglutinin (HA), which is an important target for drugs and vaccines in influenza treatment, have been revisited by ProBiS. For the first time, the identification of conserved binding sites by local structural alignment across all subtypes and strains of HA available in PDB is presented. ProBiS finds three distinctive conserved sites on HA's structure (named Site 1, Site 2, and Site 3). Compared to other predictors, ProBiS is the only one that accurately defines the receptor binding site (Site 1). Apart from that, Site 2, which is located slightly above the TBHQ binding site, is proposed as a potential novel conserved target for membrane fusion inhibitor. Lastly, Site 3, located around Helix A at the stem domain and recently targeted by cross-reactive antibodies, is predicted to be conserved in the latest H7N9 China 2013 strain as well. The further exploration of these three sites provides valuable insight in optimizing the influenza drug and vaccine development.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/physiology
Fulltext Simvastatin modulates cellular components in influenza A virus-infected cells

Mehrbod P, Hair-Bejo M, Tengku Ibrahim TA, Omar AR, El Zowalaty M, Ajdari Z, et al.

Int J Mol Med, 2014 Jul;34(1):61-73.
PMID: 24788303 DOI: 10.3892/ijmm.2014.1761

Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Continuous antigenic changes and lack of promising vaccines are the reasons for the unsuccessful treatment of influenza. Statins are pleiotropic drugs that have recently served as anti-influenza agents due to their anti-inflammatory activity. In this study, the effect of simvastatin on influenza A-infected cells was investigated. Based on the MTT cytotoxicity test, hemagglutination (HA) assay and qPCR it was found that simvastatin maintained cell viability and decreased the viral load significantly as compared to virus-inoculated cells. The expression of important pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), which was quantified using ELISA showed that simvastatin decreased the expression of pro-inflammatory cytokines to an average of 2-fold. Furthermore, the modulation of actin filament polymerization was determined using rhodamine staining. Endocytosis and autophagy processes were examined by detecting Rab and RhoA GTPase protein prenylation and LC3 lipidation using western blotting. The results showed that inhibiting GTPase and LC3 membrane localization using simvastatin inhibits influenza replication. Findings of this study provide evidence that modulation of RhoA, Rabs and LC3 may be the underlying mechanisms for the inhibitory effects of simvastatin as an anti-influenza compound.

Matched MeSH terms: Influenza A Virus, H1N1 Subtype/physiology