Collaborating Center for Reference and Research on Influenza

North Melbourne, Australia

Collaborating Center for Reference and Research on Influenza

North Melbourne, Australia
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Tate M.D.,University of Melbourne | Job E.R.,University of Melbourne | Brooks A.G.,University of Melbourne | Reading P.C.,University of Melbourne | Reading P.C.,Collaborating Center for Reference and Research on Influenza
Virology | Year: 2011

Collectins in airway fluids and membrane-associated lectins such as the macrophage mannose receptor (MMR) recognize mannose-rich glycans on the envelope glycoproteins of influenza A viruses. In this study, we used a reverse genetic approach to examine the role of particular N-linked glycosylation sites on the hemagglutinin (HA) of A/Beijing/353/89 (Beij/89, H3N2) in determining sensitivity to lectin-mediated immune defenses and virulence in mice. We generated 7:1 reassortant viruses on an A/PR/8/34 backbone with Beij/89 HA or HA lacking one or more glycosylation sites. Asn165 was an important determinant of sensitivity to mouse collectins and virulence but did not alter susceptibility of airway macrophages to infection. Removal of both Asn165 and Asn246 led to a further increase in virulence, characterized by enhanced virus replication, pulmonary inflammation and vascular leak. These studies define the importance of particular glycans on H3 HA in determining sensitivity to airway collectins and virulence in mice. © 2011 Elsevier Inc.

Ng W.C.,University of Melbourne | Liong S.,University of Melbourne | Liong S.,Mercy Hospital for Women | Tate M.D.,University of Melbourne | And 7 more authors.
Journal of Virology | Year: 2014

Specific protein receptors that mediate internalization and entry of influenza A virus (IAV) have not been identified for any cell type. Sialic acid (SIA), the primary attachment factor for IAV hemagglutinin, is expressed by numerous cell surface glycoproteins and glycolipids, confounding efforts to identify specific receptors involved in virus infection. Lec1 Chinese hamster ovary (CHO) epithelial cells express cell surface SIA and bind IAV yet are largely resistant to infection. Here, we demonstrate that expression of the murine macrophage galactose-type lectin 1 (MGL1) by Lec1 cells enhanced Ca2+-dependent IAV binding and restored permissivity to infection. Lec1 cells expressing MGL1 were infected in the presence or absence of cell surface SIA, indicating that MGL1 can act as a primary receptor or as a coreceptor with SIA. Lec1 cells expressing endocytosis-deficient MGL1 mediated Ca2+-dependent IAV binding but were less sensitive to IAV infection, indicating that direct internalization via MGL1 can result in cellular infection. Together, these studies identify MGL1 as a cell surface glycoprotein that can act as an authentic receptor for both attachment and infectious entry of IAV. © 2014, American Society for Microbiology.

Deng Y.-M.,Collaborating Center for Reference and Research on Influenza | Caldwell N.,Collaborating Center for Reference and Research on Influenza | Barr I.G.,Collaborating Center for Reference and Research on Influenza | Barr I.G.,Monash University
PLoS ONE | Year: 2011

Background: Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. Methodology/Principal Findings: A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. Conclusions/Significance: In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches. © 2011 Deng et al.

Sullivan S.G.,University of California at Los Angeles | Sullivan S.G.,Collaborating Center for Reference and Research on Influenza | Greenland S.,University of California at Los Angeles
International Journal of Epidemiology | Year: 2013

Bayesian methods have been found to have clear utility in epidemiologic analyses involving sparse-data bias or considerable background information. Easily implemented methods for conducting Bayesian analyses by data augmentation have been previously described but remain in scant use. Thus, we provide guidance on how to do these analyses with ordinary regression software. We describe in detail and provide code for the implementation of data augmentation for Bayesian and semi-Bayes regression in SAS ® software, and illustrate their use in a real logistic-regression analysis. For comparison, the same model was fitted using the Markov-chain Monte Carlo (MCMC) procedure. The two methods required a similar number of steps and yielded similar results, although for the main example, data augmentation ran in about 0.5% of the time required for MCMC. We also provide online appendices with details and examples for conditional logistic, Poisson and Cox proportional-hazards regression. © The Author 2012; all rights reserved.

Laurie K.L.,Collaborating Center for Reference and Research on Influenza | Carolan L.A.,Collaborating Center for Reference and Research on Influenza | Middleton D.,Australian Animal Health Laboratory | Lowther S.,Australian Animal Health Laboratory | And 2 more authors.
Journal of Infectious Diseases | Year: 2010

Background. An age bias toward children and young adults has been reported for infection and hospitalizations with pandemic H1N1 influenza (A[H1N1]pdm) in the 2009 and 2010 influenza seasons in the Southern and Northern Hemispheres. Serological analysis of prepandemic samples has shown a higher incidence of cross-reactive antibodies to A(H1N1)pdm virus in older populations; conserved T cell epitopes between viruses have been identified. The contribution of preexisting immunity to seasonal influenza to protection against A(H1N1)pdm infection was analyzed in a ferret model. Methods. Ferrets were pre-infected with influenza A viruses and/or vaccinated with inactivated influenza viruses with adjuvant. Infection after challenge was assessed by measuring shedding virus, transmission to naive animals, and seroconversion. Results. Homologous vaccination reduced the incidence of infection and delayed transmission. Pre-infection with virus induced sterilizing immunity to homologous challenge. One prior infection with seasonal influenza A virus improved clearance of A(H1N1)pdm virus. Prior infection with A(H1N1)pdm virus reduced shedding after seasonal influenza A challenge. Two infections with seasonal influenza A viruses reduced the incidence of infection, the amount and duration of virus shedding, and the frequency of transmission following A(H1N1)pdm challenge. Conclusion. These data suggest the reduced incidence and severity of infection with A(H1N1)pdm virus in the adult population during the 2009-2010 influenza season may be a result of previous exposure to seasonal influenza A viruses. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Sullivan S.G.,Collaborating Center for Reference and Research on Influenza | Kelly H.,Victorian Infectious Diseases Reference Laboratory | Kelly H.,Australian National University
Eurosurveillance | Year: 2013

Twice each year the World Health Organization makes a recommendation for the composition of the influenza vaccine, based on circulating strains of influenza A(H3N2), A(H1N1) and B. Strain selection has always been based on immunogenicity studies with limited human data. Immunogenicity can be considered as a proxy for vaccine effectiveness (VE). However, only interim VE estimates for the target hemisphere can be considered in time for the strain selection meeting. Using surveillance data from Victoria, Australia, we retrospectively estimated and compared interim and final VE estimates for 2007 to 2012. In general, interim estimates were within five percentage points of final estimates. However, estimates made too early or in years of low influenza activity may be unreliable. © 2007-2013. All rights reserved.

Sullivan S.G.,Collaborating Center for Reference and Research on Influenza | Tay E.L.,Victorian Infectious Diseases Reference Laboratory | Tay E.L.,Australian National University | Kelly H.,Victorian Infectious Diseases Reference Laboratory | Kelly H.,Australian National University
Vaccine | Year: 2013

Vaccine effectiveness (VE) studies are often made for a "season" which may refer to different analysis periods in different systems. We examined whether the use of four different definitions of season would materially affect estimates of influenza VE using data from the Victorian general practice sentinel surveillance network for 2007-2012. In general, the choice of analysis period had little effect on VE estimates (≤five percentage points) when there was a statistically significant protective effect of vaccination (2007, 2010 and 2012). In contrast, for years when the analysis period varied widely depending on the method used and when VE estimates were imprecise, the change in VE estimate was as much as 43 percentage points (2008). Studies of influenza VE should clearly define the analysis period used and, where possible, provide sensitivity analyses to align this definition with other VE studies. © 2013 Elsevier Ltd.

Londrigan S.L.,University of Melbourne | Tate M.D.,University of Melbourne | Tate M.D.,Monash Institute of Medical Research | Brooks A.G.,University of Melbourne | And 2 more authors.
Journal of Leukocyte Biology | Year: 2012

Airway MFF{cyrillic} and DCs are important components of innate host defense and can play a critical role in limiting the severity of influenza virus infection. Although it has been well established that cell-surface SA acts as a primary attachment receptor for IAV, the particular receptors) or coreceptor(s) that mediate IAV entry into any cell, including MFF{cyrillic} and DC, have not been clearly defined. Identifying which receptors are involved in attachment and entry of IAV into immune cells may have important implications in regard to understanding IAV tropism and pathogenesis. Recent evidence suggests that specialized receptors on MFF{cyrillic} and DCs, namely CLRs, can act as capture and/or entry receptors for many viral pathogens, including IAV. Herein, we review the early stages of infection of MFF{cyrillic} and DC by IAV. Specifically, we examine the potential role of CLRs expressed on MFF{cyrillic} and DC to act as attachment and/or entry receptors for IAV. © Society for Leukocyte Biology.

Tate M.D.,University of Melbourne | Brooks A.G.,Collaborating Center for Reference and Research on Influenza | Reading P.C.,University of Melbourne | Reading P.C.,Collaborating Center for Reference and Research on Influenza
Microbes and Infection | Year: 2011

The mouse-adapted A/PR/8/34 (PR8; H1N1) virus infects airway macrophages poorly and is virulent in mice. Herein, we have investigated factors contributing to the ability of PR8 to evade murine macrophages. We demonstrate that the hemagglutinin of PR8 binds preferentially to α(2,3)-linked sialic acid (SA) and that murine macrophages express α(2,6)-linked SA. Moreover, resialylation of macrophages to express α(2,3)-linked SA restored susceptibility to PR8. Thus, during adaptation of human influenza viruses to growth in mice, a switch in receptor specificity from α(2,6)-linked SA to α(2,3)-linked SA is likely to favour evasion of attachment, entry and destruction by airway macrophages. © 2010 Institut Pasteur.

Hurt A.C.,Collaborating Center for Reference and Research on Influenza
Current Opinion in Virology | Year: 2014

Significant changes in the circulation of antiviral-resistant influenza viruses have occurred over the last decade. The emergence and continued circulation of adamantane-resistant A(H3N2) and A(H1N1)pdm09 viruses mean that the adamantanes are no longer recommended for use. Resistance to the newer class of drugs, the neuraminidase inhibitors, is typically associated with poorer viral replication and transmission. But 'permissive' mutations, that compensated for impairment of viral function in A(H1N1) viruses during 2007/2008, enabled them to acquire the H275Y NA resistance mutation without fitness loss, resulting in their rapid global spread. Permissive mutations now appear to be present in A(H1N1)pdm09 viruses thereby increasing the risk that oseltamivir-resistant A(H1N1)pdm09 viruses may also spread globally, a concerning scenario given that oseltamivir is the most widely used influenza antiviral.

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