ORCID Profile
0000-0003-2177-8308
Current Organisation
WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity
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Publisher: MDPI AG
Date: 14-03-2014
DOI: 10.3390/V6031294
Publisher: Public Library of Science (PLoS)
Date: 24-06-2015
Publisher: Public Library of Science (PLoS)
Date: 19-08-2011
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.VACCINE.2016.08.067
Abstract: A record number of laboratory-confirmed influenza cases were notified in Australia in 2015, during which type A(H3) and type B Victoria and Yamagata lineages co-circulated. We estimated effectiveness of the 2015 inactivated seasonal influenza vaccine against specific virus lineages and clades. Three sentinel general practitioner networks conduct surveillance for laboratory-confirmed influenza amongst patients presenting with influenza-like illness in Australia. Data from the networks were pooled to estimate vaccine effectiveness (VE) for seasonal trivalent influenza vaccine in Australia in 2015 using the case test-negative study design. There were 2443 eligible patients included in the study, of which 857 (35%) were influenza-positive. Thirty-three and 19% of controls and cases respectively were reported as vaccinated. Adjusted VE against all influenza was 54% (95% CI: 42, 63). Antigenic characterisation data suggested good match between vaccine and circulating strains of A(H3) however VE for A(H3) was low at 44% (95% CI: 21, 60). Phylogenetic analysis indicated most circulating viruses were from clade 3C.2a, rather than the clade included in the vaccine (3C.3a). VE point estimates were higher against B/Yamagata lineage influenza (71% 95% CI: 57, 80) than B/Victoria (42%, 95% CI: 13, 61), and in younger people. Overall seasonal vaccine was protective against influenza infection in Australia in 2015. Higher VE against the B/Yamagata lineage included in the trivalent vaccine suggests that more widespread use of quadrivalent vaccine could have improved overall effectiveness of influenza vaccine. Genetic characterisation suggested lower VE against A(H3) influenza was due to clade mismatch of vaccine and circulating viruses.
Publisher: Elsevier BV
Date: 08-2021
Publisher: American Society for Microbiology
Date: 11-2016
DOI: 10.1128/JVI.01404-16
Abstract: Avian influenza virus (AIV) surveillance in Antarctica during 2013 revealed the prevalence of evolutionarily distinct influenza viruses of the H11N2 subtype in Adélie penguins. Here we present results from the continued surveillance of AIV on the Antarctic Peninsula during 2014 and 2015. In addition to the continued detection of H11 subtype viruses in a snowy sheathbill during 2014, we isolated a novel H5N5 subtype virus from a chinstrap penguin during 2015. Gene sequencing and phylogenetic analysis revealed that the H11 virus detected in 2014 had a .1% nucleotide similarity to the H11N2 viruses isolated in 2013, suggesting the continued prevalence of this virus in Antarctica over multiple years. However, phylogenetic analysis of the H5N5 virus showed that the genome segments were recently introduced to the continent, except for the NP gene, which was similar to that in the endemic H11N2 viruses. Our analysis indicates geographically erse origins for the H5N5 virus genes, with the majority of its genome segments derived from North American lineage viruses but the neuraminidase gene derived from a Eurasian lineage virus. In summary, we show the persistence of AIV lineages in Antarctica over multiple years, the recent introduction of gene segments from erse regions, and reassortment between different AIV lineages in Antarctica, which together significantly increase our understanding of AIV ecology in this fragile and pristine environment. IMPORTANCE Analysis of avian influenza viruses (AIVs) detected in Antarctica reveals both the relatively recent introduction of an H5N5 AIV, predominantly of North American-like origin, and the persistence of an evolutionarily ergent H11 AIV. These data demonstrate that the flow of viruses from North America may be more common than initially thought and that, once introduced, these AIVs have the potential to be maintained within Antarctica. The future introduction of AIVs from North America into the Antarctic Peninsula is of particular concern given that highly pathogenic H5Nx viruses have recently been circulating among wild birds in parts of Canada and the Unites States following the movement of these viruses from Eurasia via migratory birds. The introduction of a highly pathogenic influenza virus in penguin colonies within Antarctica might have devastating consequences.
Publisher: Public Library of Science (PLoS)
Date: 24-06-2011
Publisher: Springer Science and Business Media LLC
Date: 22-04-2015
Publisher: Wiley
Date: 17-09-2010
DOI: 10.1002/JMV.21892
Abstract: Relatively few international comparisons of the incidence of influenza related to climate parameters have been performed, particularly in the Eastern hemisphere. In this study, the incidence of influenza and climate data such as temperature, relative humidity, and rainfall, from cities at different latitudes with contrasting climates: Singapore, Hong Kong (China), Ulaanbaatar (Mongolia), Vancouver (Canada), and three Australian cities (Brisbane, Melbourne and Sydney) were examined to determine whether there was any overall relationship between the incidence of influenza and climate. Applying time-series analyses to the more comprehensive datasets, it was found that relative humidity was associated with the incidence of influenza A in Singapore, Hong Kong, Brisbane, and Vancouver. In the case of influenza B, the mean temperature was the key climate variable associated with the incidence of influenza in Hong Kong, Brisbane, Melbourne, and Vancouver. Rainfall was not significantly correlated with the incidence of influenza A or B in any of these cities.
Publisher: American Society for Microbiology
Date: 12-2017
DOI: 10.1128/JCM.00957-17
Abstract: Influenza A and B viruses are the causative agents of annual influenza epidemics that can be severe, and influenza A viruses intermittently cause pandemics. Sequence information from influenza virus genomes is instrumental in determining mechanisms underpinning antigenic evolution and antiviral resistance. However, due to sequence ersity and the dynamics of influenza virus evolution, rapid and high-throughput sequencing of influenza viruses remains a challenge. We developed a single-reaction influenza A/B virus (FluA/B) multiplex reverse transcription-PCR (RT-PCR) method that lifies the most critical genomic segments (hemagglutinin [HA], neuraminidase [NA], and matrix [M]) of seasonal influenza A and B viruses for next-generation sequencing, regardless of viral type, subtype, or lineage. Herein, we demonstrate that the strategy is highly sensitive and robust. The strategy was validated on thousands of seasonal influenza A and B virus-positive specimens using multiple next-generation sequencing platforms.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JCV.2015.04.019
Abstract: Full genome sequencing of influenza A viruses (IAV), including those that arise from annual influenza epidemics, is undertaken to determine if reassorting has occurred or if other pathogenic traits are present. Traditionally IAV sequencing has been biased toward the major surface glycoproteins haemagglutinin and neuraminidase, while the internal genes are often ignored. Despite the development of next generation sequencing (NGS), many laboratories are still reliant on conventional Sanger sequencing to sequence IAV. To develop a minimal and robust set of primers for Sanger sequencing of the full genome of IAV currently circulating in humans. A set of 13 primer pairs was designed that enabled lification of the six internal genes of multiple human IAV subtypes including the recent avian influenza A(H7N9) virus from China. Specific primers were designed to lify the HA and NA genes of each IAV subtype of interest. Each of the primers also incorporated a binding site at its 5'-end for either a forward or reverse M13 primer, such that only two M13 primers were required for all subsequent sequencing reactions. This minimal set of primers was suitable for sequencing the six internal genes of all currently circulating human seasonal influenza A subtypes as well as the avian A(H7N9) viruses that have infected humans in China. This streamlined Sanger sequencing protocol could be used to generate full genome sequence data more rapidly and easily than existing influenza genome sequencing protocols.
Publisher: The American Association of Immunologists
Date: 03-2013
Abstract: Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the viral hemagglutinin (HA). Glycans on the head of HA promote virus survival by shielding antigenic sites, but highly glycosylated seasonal IAV are inactivated by soluble lectins of the innate immune system. In 2009, human strains of pandemic H1N1 [A(H1N1)pdm] expressed a single glycosylation site (Asn104) on the head of HA. Since then, variants with additional glycosylation sites have been detected, and the location of these sites has been distinct to those of recent seasonal H1N1 strains. We have compared wild-type and reverse-engineered A(H1N1)pdm IAV with differing potential glycosylation sites on HA for sensitivity to collectins and to neutralizing Abs. Addition of a glycan (Asn136) to A(H1N1)pdm HA was associated with resistance to neutralizing Abs but did not increase sensitivity to collectins. Moreover, variants expressing Asn136 showed enhanced growth in A(H1N1)pdm-vaccinated mice, consistent with evasion of Ab-mediated immunity in vivo. Thus, a fine balance exists regarding the optimal pattern of HA glycosylation to facilitate evasion of Ab-mediated immunity while maintaining resistance to lectin-mediated defenses of the innate immune system.
Publisher: Frontiers Media SA
Date: 2015
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 26-10-2017
DOI: 10.2807/1560-7917.ES.2017.22.43.17-00707
Abstract: In 2017, influenza seasonal activity was high in the southern hemisphere. We present interim influenza vaccine effectiveness (VE) estimates from Australia. Adjusted VE was low overall at 33% (95% confidence interval (CI): 17 to 46), 50% (95% CI: 8 to 74) for A(H1)pdm09, 10% (95% CI: -16 to 31) for A(H3) and 57% (95% CI: 41 to 69) for influenza B. For A(H3), VE was poorer for those vaccinated in the current and prior seasons.
Publisher: American Society for Microbiology
Date: 15-03-2011
DOI: 10.1128/JVI.01705-10
Abstract: It is widely recognized that sialic acid (SA) can mediate attachment of influenza virus to the cell surface, and yet the specific receptors that mediate virus entry are not known. For many viruses, a definitive demonstration of receptor function has been achieved when nonpermissive cells are rendered susceptible to infection following transfection of the gene encoding a putative receptor. For influenza virus, such approaches have been confounded by the abundance of SA on mammalian cells so that it has been difficult to identify cell lines that are not susceptible to infection. We examined influenza virus infection of Lec2 Chinese hamster ovary (CHO) cells, a mutant cell line deficient in SA. Lec2 CHO cells were resistant to influenza virus infection, and stable cell lines expressing either DC-SIGN or L-SIGN were generated to assess the potential of each molecule to function as SA-independent receptors for influenza A viruses. Virus strain BJx109 (H3N2) bound to Lec2 CHO cells expressing DC-SIGN or L-SIGN in a Ca 2+ -dependent manner, and transfected cells were susceptible to virus infection. Treatment of Lec2-DC-SIGN and Lec2-L-SIGN cells with mannan, but not bacterial neuraminidase, blocked infection, a finding consistent with SA-independent virus attachment and entry. Moreover, virus strain PR8 (H1N1) bears low levels of mannose-rich glycans and was inefficient at infecting Lec2 CHO cells expressing either DC-SIGN or L-SIGN, whereas other glycosylated H1N1 subtype viruses could infect cells efficiently. Together, these data indicate that human C-type lectins (DC-SIGN and L-SIGN) can mediate attachment and entry of influenza viruses independently of cell surface SA.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.ANTIVIRAL.2008.06.008
Abstract: The adamantanes (amantadine and rimantadine) were the initial antivirals licensed for use against influenza A viruses and have been used in some countries to control seasonal influenza and have also been stockpiled for potential pandemic use. While high rates of resistance have been observed in recent years with A(H3) viruses, the rates of resistance with A(H1) viruses has varied widely. In this study we analysed 281 human influenza A viruses isolated in 2007 that were referred to the WHO Collaborating Centre for Reference and Research in Melbourne, mainly from Australia and the surrounding regions, for evidence of resistance to adamantanes and a subset of these was examined for resistance to the neuraminidase inhibitors (NIs). We found that the rates of adamantane resistance in A(H3) viruses continued to increase in most countries in 2007 but a distinct variation was seen with A(H1) resistance levels. A(H1) viruses from Australia, New Zealand and Europe had low rates of resistance (2-9%) whereas viruses from a number of South East (SE) Asian countries had high rates of resistance (33-100%). This difference can be attributed to the spread of A/Brisbane/59/2007-like viruses to many parts of the world with the exception of SE Asia where A/Hong Kong/2652/2006-like viruses continue to predominate. When these two A(H1) subgroups were compared for their in vitro sensitivity to the other class of influenza antiviral drugs, the neuraminidase inhibitors, no difference was seen between the groups with both showing normal levels of sensitivity to these drugs, The finding of reducing A(H1) resistance rates in Australia and rising levels in SE Asia in 2007, reverses the trend seen in 2006 when A(H1) resistance levels were rising in Australia and elsewhere but remained low in most of SE Asia.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 1999
DOI: 10.1016/S0168-1656(98)00175-8
Abstract: A plasmid-encoded phage abortive infection mechanism (AbiL) was identified from Lactococcus lactis biovar. diacetylactis LD10-1. AbiL conferred complete resistance to the small isometric-headed phage phi 712 (936 species) and partial resistance to the prolate-headed phage phi c2 (c2 species) when introduced into L. lactis LM0230. However, AbiL was not effective against the small isometric-headed phage ul36 (P335 species). The AbiL determinant was sequenced and it consists of two open reading frames, abiLi and abiLii. Their encoded proteins did not share significant homology with any known proteins in the protein databases. Transcriptional analysis indicated that abiLi and abiLii are organized as a single operon. Deletion within abiLii abolished the phage resistance. The levels of four phi c2-specific transcripts, three within the early transcribed region and one within the late transcribed region, were examined by RT-PCR, no effect of AbiL on synthesis of these transcripts was detected, suggesting that AbiL may act at a point after the transcription of phi c2 in L. lactis.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.MEEGID.2019.103920
Abstract: The persistent circulation of avian influenza viruses (AIVs) is an ongoing problem for many countries in South East Asia, causing large economic losses to both the agricultural and health sectors. This review analyses AIV ersity, evolution and the risk of AIV emergence in humans in countries of the Greater Mekong Subregion (GMS): Cambodia, Laos, Myanmar, Thailand and Vietnam (excluding China). The analysis was based on AIV sequencing data, serological studies, published journal articles and AIV outbreak reports available from January 2003 to December 2018. All countries of the GMS have suffered losses due repeated outbreaks of highly pathogenic (HP) H5N1 that has also caused human cases in all GMS countries. In Laos, Myanmar and Vietnam AIV outbreaks in domestic poultry have also been caused by clade 2.3.4.4 H5N6. A erse range of low pathogenic AIVs (H1-H12) have been detected in poultry and wild bird species, though surveillance for and characterization of these subtypes is limited. Subtype H3, H4, H6 and H11 viruses have been detected over prolonged periods whilst H1, H2, H7, H8, H10 and H12 viruses have only been detected transiently. H9 AIVs circulate endemically in Cambodia and Vietnam with seroprevalence data indicating human exposure to H9 AIVs in Cambodia, Thailand and Vietnam. As surveillance studies focus heavily on the detection of H5 AIVs in domestic poultry further research is needed to understand the true level of AIV ersity and the risk AIVs pose to humans in the GMS.
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 23-11-2017
DOI: 10.2807/1560-7917.ES.2017.22.47.17-00731
Abstract: For over a decade virtually all A(H3N2) influenza viruses have been resistant to the adamantane class of antivirals. However, during the 2017 influenza season in Australia, 15/461 (3.3%) adamantane-sensitive A(H3N2) viruses encoding serine at residue 31 of the M2 protein were detected, more than the total number identified globally during the last 6 years. A return to wide circulation of adamantane-sensitive A(H3N2) viruses would revive the option of using these drugs for treatment and prophylaxis.
Publisher: American Society for Microbiology
Date: 15-09-2013
DOI: 10.1128/JVI.03437-12
Abstract: Influenza A H10N7 virus with a hemagglutinin gene of North American origin was detected in Australian chickens and poultry abattoir workers in New South Wales, Australia, in 2010 and in chickens in Queensland, Australia, on a mixed chicken and domestic duck farm in 2012. We investigated their genomic origins by sequencing full and partial genomes of H10 viruses isolated from wild aquatic birds and poultry in Australia and analyzed them with all available avian influenza virus sequences from Oceania and representative viruses from North America and Eurasia. Our analysis showed that the H10N7 viruses isolated from poultry were similar to those that have been circulating since 2009 in Australian aquatic birds and that their initial transmission into Australia occurred during 2007 and 2008. The H10 viruses that appear to have developed endemicity in Australian wild aquatic birds were derived from several viruses circulating in waterfowl along various flyways. Their hemagglutinin gene was derived from aquatic birds in the western states of the United States, whereas the neuraminidase was closely related to that from viruses previously detected in waterfowl in Japan. The remaining genes were derived from Eurasian avian influenza virus lineages. Our analysis of virological data spanning 40 years in Oceania indicates that the long-term evolutionary dynamics of avian influenza viruses in Australia may be determined by climatic changes. The introduction and long-term persistence of avian influenza virus lineages were observed during periods with increased rainfall, whereas bottlenecks and extinction were observed during phases of widespread decreases in rainfall. These results extend our understanding of factors affecting the dynamics of avian influenza and provide important considerations for surveillance and disease control strategies.
Publisher: The American Association of Immunologists
Date: 10-2010
Abstract: Acquired immune responses elicited to recent strains of seasonal H1N1 influenza viruses provide limited protection against emerging A(H1N1) pandemic viruses. Accordingly, pre-existing or rapidly induced innate immune defenses are of critical importance in limiting early infection. Respiratory secretions contain proteins of the innate immune system, including members of the collectin and pentraxin superfamilies. These mediate potent antiviral activity and act as an initial barrier to influenza infection. In this study, we have examined the sensitivity of H1N1 viruses, including pandemic virus strains, for their sensitivity to collectins (surfactant protein [SP]-D and mannose-binding lectin [MBL]) and to the pentraxin PTX3. Human SP-D and MBL inhibited virus-induced hemagglutinating activity, blocked the enzymatic activity of the viral neuraminidase, and neutralized the ability of H1N1 viruses to infect human respiratory epithelial cells in a manner that correlated with the degree of glycosylation in the globular head of the hemagglutinin. Recent seasonal H1N1 viruses expressed three to four N-glycosylation sequons on the head of hemagglutinin and were very sensitive to inhibition by SP-D or MBL, whereas A(H1N1) pandemic viruses expressed a single N-glycosylation sequon and were resistant to either collectin. Of interest, both seasonal and pandemic H1N1 viruses were resistant to PTX3. Thus, unlike recent seasonal H1N1 strains of influenza virus, A(H1N1) pandemic viruses are resistant to the antiviral activities of innate immune proteins of the collectin superfamily.
Publisher: Informa UK Limited
Date: 2000
DOI: 10.3109/10425170009033237
Abstract: A plasmid-encoded type I restriction and modification (R-M) system, designated LldI, was identified in Lactococcus lactis biovar diacetylactis LD10-1. LldI consists of three genes encoding endonuclease, methylase and specificity subunits, respectively. RT-PCR analysis revealed that the three genes are co-transcribed as a polycistronic mRNA in L. lactis. The specificity subunit of LldI differs significantly in the target recognition domains from those of other type I R-M systems, suggesting that LldI confers a novel specificity in L. lactis.
Publisher: The American Association of Immunologists
Date: 2014
Abstract: The long pentraxin, pentraxin 3 (PTX3), can play beneficial or detrimental roles during infection and disease by modulating various aspects of the immune system. There is growing evidence to suggest that PTX3 can mediate antiviral activity in vitro and in vivo. Previous studies demonstrated that PTX3 and the short pentraxin serum amyloid P express sialic acids that are recognized by the hemagglutinin (HA) glycoprotein of certain influenza A viruses (IAV), resulting in virus neutralization and anti-IAV activity. In this study, we demonstrate that specificity of both HA and the viral neuraminidase for particular sialic acid linkages determines the susceptibility of H1N1, H3N2, and H7N9 strains to the antiviral activities of PTX3 and serum amyloid P. Selection of H3N2 virus mutants resistant to PTX3 allowed for identification of amino acid residues in the vicinity of the receptor-binding pocket of HA that are critical determinants of sensitivity to PTX3 this was supported by sequence analysis of a range of H3N2 strains that were sensitive or resistant to PTX3. In a mouse model of infection, the enhanced virulence of PTX3-resistant mutants was associated with increased virus replication and elevated levels of proinflammatory cytokines in the airways, leading to pulmonary inflammation and lung injury. Together, these studies identify determinants in the viral HA that can be associated with sensitivity to the antiviral activities of PTX3 and highlight its importance in the control of IAV infection.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JCV.2017.10.018
Abstract: The isolation and propagation of influenza viruses from clinical specimens are essential tools for comprehensive virologic surveillance. Influenza viruses must be lified in cell culture for detailed antigenic analysis and for phenotypic assays assessing susceptibility to antiviral drugs or for other assays. To conduct an external quality assessment (EQA) of proficiency for isolation and identification of influenza viruses using cell culture techniques among National Influenza Centres (NICs) in the World Health Organisation (WHO) South East Asia and Western Pacific Regions. Twenty-one NICs performed routine influenza virus isolation and identification techniques on a proficiency testing panel comprising 16 s les, containing influenza A or B viruses and negative control s les. One s le was used exclusively to determine their capacity to measure hemagglutination titer and the other 15 s les were used for virus isolation and identification. All NICs performed influenza virus isolation using Madin Darby canine kidney (MDCK) or MDCK-SIAT-1 cells. If virus growth was detected, the type, subtype and/or lineage of virus present in isolates was determined using immunofluorescence, RT-PCR and/or hemagglutination inhibition (HI) assays. Most participating laboratories could detect influenza virus growth and could identify virus lified from EQA s les. However, some laboratories failed to isolate and identify viruses from EQA s les that contained lower titres of virus, highlighting issues regarding the sensitivity of influenza virus isolation methods between laboratories. This first round of EQA was successfully conducted by NICs in the Asia Pacific Region, revealing good proficiency in influenza virus isolation and identification.
Publisher: Wiley
Date: 15-02-2012
Publisher: Elsevier BV
Date: 09-2002
DOI: 10.1016/S0378-1119(02)00918-6
Abstract: A plasmid-borne copper resistance operon (lco) was identified from Lactococcus lactis subsp. lactis LL58-1. The lco operon consists of three structural genes lcoABC. The predicted products of lcoA and lcoB were homologous to chromosomally encoded prolipoprotein diacylglyceral transferases and two uncharacterized proteins respectively, and the product of lcoC is similar to several multicopper oxidases, which are generally plasmid-encoded. This genetic organization represents a new combination of genes for copper resistance in bacteria. The three genes are co-transcribed from a copper-inducible promoter, which is controlled by lcoRS encoding a response regulator and a kinase sensor. The five genes are flanked by two insertion sequences, almost identical to IS-LL6 from L. lactis. Transposon mutagenesis and subcloning analysis indicated that the three structural genes were all required for copper resistance. Copper assay results showed that the extracellular concentration of copper of L. lactis LM0230 containing the lco operon was significantly higher than that of the host strain when copper was added at concentrations from 2 to 3 mM. The results suggest that the lco operon conferred copper resistance by reducing the intracellular accumulation of copper ions in L. lactis.
Publisher: eLife Sciences Publications, Ltd
Date: 16-01-2015
DOI: 10.7554/ELIFE.05055
Abstract: A complex interplay of viral, host, and ecological factors shapes the spatio-temporal incidence and evolution of human influenza viruses. Although considerable attention has been paid to influenza A viruses, a lack of equivalent data means that an integrated evolutionary and epidemiological framework has until now not been available for influenza B viruses, despite their significant disease burden. Through the analysis of over 900 full genomes from an epidemiological collection of more than 26,000 strains from Australia and New Zealand, we reveal fundamental differences in the phylodynamics of the two co-circulating lineages of influenza B virus (Victoria and Yamagata), showing that their in idual dynamics are determined by a complex relationship between virus transmission, age of infection, and receptor binding preference. In sum, this work identifies new factors that are important determinants of influenza B evolution and epidemiology.
Publisher: Wiley
Date: 23-07-2016
DOI: 10.1111/IRV.12402
Publisher: Springer Science and Business Media LLC
Date: 22-08-2017
Publisher: Elsevier BV
Date: 2002
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-09-2023
Publisher: Springer Science and Business Media LLC
Date: 19-04-2011
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 05-2012
Publisher: Oxford University Press (OUP)
Date: 2005
DOI: 10.1111/J.1365-2672.2004.02441.X
Abstract: To develop food-grade cloning and expression vectors for use in genetic modification of Lactococcus lactis. Two plasmid replicons and three dominant selection markers were isolated from L. lactis and used to construct five food-grade cloning vectors. These vectors were composed of DNA only from L. lactis and contained no antibiotic resistance markers. Three of the vectors (pND632, pND648 and pND969) were based on the same plasmid replicon and carried, either alone or in combination, the three different selectable markers encoding resistance to nisin, cadmium and/or copper. The other two (pND965DJ and pND965RS) were derived from a cadmium resistance plasmid, and carried a constitutive promoter and a copper-inducible promoter, respectively, immediately upstream of a multicloning site. All vectors were stable in L. lactis LM0230 for at least 40 generations without selection pressure. The two groups of vectors were compatible in L. lactis LM0230. The vectors pND648 and pND965RS, as representatives of the two groups, were transferred successfully by electroporation into and maintained in an industrial strain of L. lactis. The usefulness of the vectors was further demonstrated by expressing a phage resistance gene (abiI) in another industrial strain of L. lactis. The five food-grade vectors constructed are potentially useful for industrial strains of L. lactis. These vectors represent a new set of molecular tools useful for food-grade modifications of L. lactis.
Publisher: Elsevier BV
Date: 09-1997
Abstract: The 8.8-kb Lactococcus lactis plasmid pND302 encodes resistance to cadmium (CdR). Regions of pND302 involved in replication and CdR were subcloned and sequenced. The replication region is localized on a 1.5-kb region and consists of an open reading frame (repB) preceded by a noncoding AT-rich sequence (ori) which is highly homologous to lactococcal theta-type replicons. The CdR determinant is localized on a 2.9-kb region and encodes putative proteins similar to the Cd(2+)-specific P-type efflux ATPase (CadA) and the transcriptional regulatory repressor (CadC) identified in Staphylococcus aureus, Bacillus firmus, and Listeria monocytogenes. Similar CdR determinants were also detected by PCR in other CdR plasmids isolated from different L. lactis strains.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.VIROL.2016.01.024
Abstract: Many insights regarding the pathogenesis of human influenza A virus (IAV) infections have come from studies in mice and ferrets. Surfactant protein (SP)-D is the major neutralizing inhibitor of IAV in mouse airway fluids and SP-D-resistant IAV mutants show enhanced virus replication and virulence in mice. Herein, we demonstrate that sialylated glycoproteins, rather than SP-D, represent the major neutralizing inhibitors against H3 subtype viruses in airway fluids from naïve ferrets. Moreover, while resistance to neutralizing inhibitors is a critical factor in modulating virus replication and disease in the mouse model, it does not appear to be so in the ferret model, as H3 mutants resistant to either SP-D or sialylated glycoproteins in ferret airway fluids did not show enhanced virulence in ferrets. These data have important implications for our understanding of pathogenesis and immunity to human IAV infections in these two widely used animal models of infection.
Publisher: The American Association of Immunologists
Date: 12-2009
Abstract: The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.
Location: Australia
No related grants have been discovered for Yi-Mo Deng.