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1.
J Infect Dis ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37950884

RESUMO

BACKGROUND: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. METHODS: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017/18 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016/17) standard-dose vaccination. RESULTS: Mean fold rise (MFR) in antibody titers from Day 0 to Day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017/18 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) vs. without (range, 4.3-14.3) prior 2016/17 vaccination. MFR was significantly reduced by about one half to four fifths for previously vaccinated recipients of standard-dose and all three enhanced vaccines (ß range, 0.21-0.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR vs. standard-dose vaccine by microneutralization assay. CONCLUSIONS: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.

2.
Clin Infect Dis ; 76(3): e1328-e1334, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35959938

RESUMO

BACKGROUND: Influenza circulated at historically low levels during 2020/2021 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic travel restrictions. In Australia, international arrivals were required to undergo a 14-day hotel quarantine to limit new introduction of SARS-CoV-2. METHODS: We usedtesting data for travelers arriving on repatriation flights to Darwin, Australia, from 3 January 2021 to 11 October 2021 to identify importations of influenza virus into Australia. We used this information to estimate the risk of a case exiting quarantine while still infectious. Influenza-positive samples were sequenced, and cases were followed up to identify transmission clusters. Data on the number of cases and total passengers were used to infer the risk of influenza cases exiting quarantine while infectious. RESULTS: Despite very low circulation of influenza globally, 42 cases were identified among 15 026 returned travelers, of which 30 were A(H3N2), 2 were A(H1N1)pdm09, and 10 were B/Victoria. Virus sequencing data identified potential in-flight transmission, as well as independent infections prior to travel. Under the quarantine strategy in place at the time, the probability that these cases could initiate influenza outbreaks in Australia neared 0. However, this probability rose as quarantine requirements relaxed. CONCLUSIONS: Detection of influenza virus infections in repatriated travelers provided a source of influenza viruses otherwise unavailable and enabled development of the A(H3N2) vaccine seed viruses included in the 2022 Southern Hemisphere influenza vaccine. Failure to test quarantined returned travelers for influenza represents a missed opportunity for enhanced surveillance to better inform public health preparedness.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Quarentena , Vírus da Influenza A Subtipo H3N2 , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vitória
3.
Emerg Infect Dis ; 29(1): 170-174, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36573541

RESUMO

In late 2021, highly pathogenic avian influenza A(H5N8) clade 2.3.4.4b viruses were detected in domestic ducks in poultry markets in Cambodia. Surveillance, biosafety, and biosecurity efforts should be bolstered along the poultry value chain to limit spread and infection risk at the animal-human interface.


Assuntos
Vírus da Influenza A Subtipo H5N8 , Influenza Aviária , Influenza Humana , Doenças das Aves Domésticas , Animais , Humanos , Influenza Aviária/epidemiologia , Camboja/epidemiologia , Aves , Patos , Aves Domésticas , Filogenia
4.
Euro Surveill ; 28(37)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37707981

RESUMO

BackgroundCOVID-19 pandemic mitigation measures, including travel restrictions, limited global circulation of influenza viruses. In Australia, travel bans for non-residents and quarantine requirements for returned travellers were eased in November 2021, providing pathways for influenza viruses to be re-introduced.AimWe aimed to describe the epidemiological and virological characteristics of the re-emergence of influenza in Victoria, Australia to inform public health interventions.MethodsFrom 1 November 2021 to 30 April 2022, we conducted an epidemiological study analysing case notification data from the Victorian Department of Health to describe case demographics, interviewed the first 200 cases to establish probable routes of virus reintroduction and examined phylogenetic and antigenic data to understand virus diversity and susceptibility to current vaccines.ResultsOverall, 1,598 notifications and 1,064 positive specimens were analysed. The majority of cases (61.4%) occurred in the 15-34 years age group. Interviews revealed a higher incidence of international travel exposure during the first month of case detections, and high levels of transmission in university residential colleges were associated with return to campus. Influenza A(H3N2) was the predominant subtype, with a single lineage predominating despite multiple importations.ConclusionEnhanced testing for respiratory viruses during the COVID-19 pandemic provided a more complete picture of influenza virus transmission compared with previous seasons. Returned international travellers were important drivers of influenza reemergence, as were young adults, a group whose role has previously been under-recognised in the establishment of seasonal influenza epidemics. Targeting interventions, including vaccination, to these groups could reduce future influenza transmission.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Adulto Jovem , Humanos , Vitória/epidemiologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias , Vírus da Influenza A Subtipo H3N2 , Filogenia , COVID-19/epidemiologia
5.
J Infect Dis ; 226(6): 1022-1026, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-35380689

RESUMO

We explored the potential for a biphasic pattern in waning of antibody titers after influenza vaccination. We collected blood samples in a randomized controlled trial of influenza vaccination in children and tested them with hemagglutination inhibition assays for influenza A(H3N2) and influenza B/Victoria lineage. Using piecewise log-linear mixed-effects models, we found evidence for a faster initial waning of antibody titers for the first 1-2 years after vaccination and then slower longer-term declines. Children with higher postvaccination titers had faster antibody decay.


Assuntos
Vacinas contra Influenza , Influenza Humana , Anticorpos Antivirais , Criança , Hemaglutinação , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Influenza Humana/prevenção & controle , Vacinação , Vacinas de Produtos Inativados
6.
J Virol ; 95(24): e0126721, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34586866

RESUMO

Introduction of non-pharmaceutical interventions to control COVID-19 in early 2020 coincided with a global decrease in active influenza circulation. However, between July and November 2020, an influenza A(H3N2) epidemic occurred in Cambodia and in other neighboring countries in the Greater Mekong Subregion in Southeast Asia. We characterized the genetic and antigenic evolution of A(H3N2) in Cambodia and found that the 2020 epidemic comprised genetically and antigenically similar viruses of Clade3C2a1b/131K/94N, but they were distinct from the WHO recommended influenza A(H3N2) vaccine virus components for 2020-2021 Northern Hemisphere season. Phylogenetic analysis revealed multiple virus migration events between Cambodia and bordering countries, with Laos PDR and Vietnam also reporting similar A(H3N2) epidemics immediately following the Cambodia outbreak: however, there was limited circulation of these viruses elsewhere globally. In February 2021, a virus from the Cambodian outbreak was recommended by WHO as the prototype virus for inclusion in the 2021-2022 Northern Hemisphere influenza vaccine. IMPORTANCE The 2019 coronavirus disease (COVID-19) pandemic has significantly altered the circulation patterns of respiratory diseases worldwide and disrupted continued surveillance in many countries. Introduction of control measures in early 2020 against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has resulted in a remarkable reduction in the circulation of many respiratory diseases. Influenza activity has remained at historically low levels globally since March 2020, even when increased influenza testing was performed in some countries. Maintenance of the influenza surveillance system in Cambodia in 2020 allowed for the detection and response to an influenza A(H3N2) outbreak in late 2020, resulting in the inclusion of this virus in the 2021-2022 Northern Hemisphere influenza vaccine.


Assuntos
COVID-19/epidemiologia , Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/imunologia , Influenza Humana/complicações , Influenza Humana/imunologia , Camboja/epidemiologia , Surtos de Doenças , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Laos , Funções Verossimilhança , Filogenia , SARS-CoV-2 , Vietnã
7.
PLoS Pathog ; 16(6): e1008592, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555740

RESUMO

The neuraminidase (NA) inhibitor (NAI) oseltamivir (OST) is the most widely used influenza antiviral drug. Several NA amino acid substitutions are reported to reduce viral susceptibility to OST in in vitro assays. However, whether there is a correlation between the level of reduction in susceptibility in vitro and the efficacy of OST against these viruses in vivo is not well understood. In this study, a ferret model was utilised to evaluate OST efficacy against circulating influenza A and B viruses with a range of in vitro generated 50% inhibitory concentrations (IC50) values for OST. OST efficacy against an A(H1N1)pdm09 and an A(H1N1)pdm09 virus with the H275Y substitution in neuraminidase was also tested in the macaque model. The results from this study showed that OST had a significant impact on virological parameters compared to placebo treatment of ferrets infected with wild-type influenza A viruses with normal IC50 values (~1 nM). However, this efficacy was lower against wild-type influenza B and other viruses with higher IC50 values. Differing pathogenicity of the viruses made evaluation of clinical parameters difficult, although some effect of OST in reducing clinical signs was observed with influenza A(H1N1) and A(H1N1)pdm09 (H275Y) viruses. Viral titres in macaques were too low to draw conclusive results. Analysis of the ferret data revealed a correlation between IC50 and OST efficacy in reducing viral shedding but highlighted that the current WHO guidelines/criteria for defining normal, reduced or highly reduced inhibition in influenza B viruses based on in vitro data are not well aligned with the low in vivo OST efficacy observed for both wild-type influenza B viruses and those with reduced OST susceptibility.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Infecções por Orthomyxoviridae , Oseltamivir , Animais , Feminino , Masculino , Substituição de Aminoácidos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Furões , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/metabolismo , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/metabolismo , Vírus da Influenza B/genética , Vírus da Influenza B/metabolismo , Macaca fascicularis , Macrolídeos , Mutação de Sentido Incorreto , Neuraminidase/genética , Neuraminidase/metabolismo , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Oseltamivir/farmacologia
8.
Clin Infect Dis ; 73(11): e4269-e4277, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-33175132

RESUMO

BACKGROUND: Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. METHODS: A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post-first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. RESULTS: Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P > .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2-14.9; P = .02). CONCLUSIONS: High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Anticorpos Antivirais , Austrália , Testes de Inibição da Hemaglutinação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Vacinação , Vacinas de Produtos Inativados
9.
Emerg Infect Dis ; 27(6): 1-9, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34013862

RESUMO

Human respiratory syncytial virus (HRSV) is the leading viral cause of serious pediatric respiratory disease, and lifelong reinfections are common. Its 2 major subgroups, A and B, exhibit some antigenic variability, enabling HRSV to circulate annually. Globally, research has increased the number of HRSV genomic sequences available. To ensure accurate molecular epidemiology analyses, we propose a uniform nomenclature for HRSV-positive samples and isolates, and HRSV sequences, namely: HRSV/subgroup identifier/geographic identifier/unique sequence identifier/year of sampling. We also propose a template for submitting associated metadata. Universal nomenclature would help researchers retrieve and analyze sequence data to better understand the evolution of this virus.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Variação Genética , Genótipo , Humanos , Epidemiologia Molecular , Filogenia , Vírus Sincicial Respiratório Humano/genética
10.
J Immunol ; 202(12): 3370-3380, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092636

RESUMO

The importance of antiviral CD8+ T cell recognition of alternative reading frame (ARF)-derived peptides is uncertain. In this study, we describe an epitope (NS1-ARF21-8) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF21-8 elicits a robust, highly functional CD8+ T cell response in IAV-infected BALB/c mice. NS1-ARF21-8 is presented from unspliced NS mRNA, likely from downstream initiation on a Met residue that comprises the P1 position of NS1-ARF21-8 Derived from a 14-residue peptide with no apparent biological function and negligible impacts on IAV infection, infectivity, and pathogenicity, NS1-ARF21-8 provides a clear demonstration of how immunosurveillance exploits natural errors in protein translation to provide antiviral immunity. We further show that IAV infection enhances a model cellular ARF translation, which potentially has important implications for virus-induced autoimmunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/metabolismo , Vírus da Influenza A/fisiologia , Influenza Humana/imunologia , Infecções por Orthomyxoviridae/imunologia , Proteínas não Estruturais Virais/metabolismo , Processamento Alternativo , Animais , Modelos Animais de Doenças , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Vigilância Imunológica , Camundongos , Camundongos Endogâmicos BALB C , Fases de Leitura Aberta/genética , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
11.
Nature ; 523(7559): 217-20, 2015 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-26053121

RESUMO

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.


Assuntos
Variação Antigênica , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Fatores Etários , Saúde Global , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza B/classificação , Filogenia , Filogeografia , Estações do Ano
12.
Euro Surveill ; 26(29)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34296673

RESUMO

The non-pharmaceutical interventions implemented to slow the spread of SARS-CoV-2 have had consequences on the transmission of other respiratory viruses, most notably paediatric respiratory syncytial virus (RSV) and influenza. At the beginning of 2020, lockdown measures in the southern hemisphere led to a winter season with a marked reduction in both infections. Intermittent lockdowns in the northern hemisphere also appeared to interrupt transmission during winter 2020/21. However, a number of southern and northern hemisphere countries have now seen delayed RSV peaks. We examine the implications of these unpredictable disease dynamics for health service delivery in Europe, such as paediatric hospital and intensive care bed space planning, or palivizumab prophylaxis. We discuss the challenges for RSV vaccine trials and influenza immunisation campaigns, and highlight the considerable research opportunities that have arisen with the SARS-CoV-2 pandemic. We argue that the rapid advances in viral whole genome sequencing, phylogenetic analysis, and open data sharing during the pandemic are applicable to the ongoing surveillance of RSV and influenza. Lastly, we outline actions to prepare for forthcoming influenza seasons and for future implementation of RSV vaccines.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Controle de Doenças Transmissíveis , Europa (Continente) , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Filogenia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , SARS-CoV-2
13.
Clin Infect Dis ; 71(7): 1704-1714, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31828291

RESUMO

BACKGROUND: Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. METHODS: Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. RESULTS: Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. CONCLUSIONS: In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. CLINICAL TRIALS REGISTRATION: NCT03330132.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adjuvantes Imunológicos , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais , Testes de Inibição da Hemaglutinação , Humanos , Imunogenicidade da Vacina , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/prevenção & controle , Esqualeno
14.
Emerg Infect Dis ; 26(1): 143-147, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31661057

RESUMO

In 2018, a 15-year-old female adolescent in Australia was infected with swine influenza A(H3N2) variant virus. The virus contained hemagglutinin and neuraminidase genes derived from 1990s-like human seasonal viruses and internal protein genes from influenza A(H1N1)pdm09 virus, highlighting the potential risk that swine influenza A virus poses to human health in Australia.


Assuntos
Vírus da Influenza A Subtipo H3N2 , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Adolescente , Animais , Austrália/epidemiologia , Feminino , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/etiologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Filogenia , Suínos , Doenças dos Suínos/transmissão
15.
J Biomed Sci ; 27(1): 17, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906961

RESUMO

BACKGROUND: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. RESULTS: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. CONCLUSIONS: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.


Assuntos
Evolução Molecular , Variação Genética , Vírus da Influenza A Subtipo H3N2/fisiologia , Biossíntese de Proteínas/genética , Proteínas de Ligação a RNA , Proteínas do Core Viral , Replicação Viral/genética , Células A549 , Animais , Cães , Humanos , Influenza Humana/epidemiologia , Influenza Humana/genética , Influenza Humana/metabolismo , Células Madin Darby de Rim Canino , Proteínas do Nucleocapsídeo , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética , Taiwan , Proteínas do Core Viral/biossíntese , Proteínas do Core Viral/genética
16.
Euro Surveill ; 25(25)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32613937

RESUMO

The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen's eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.


Assuntos
Galinhas/imunologia , Coronavirus/fisiologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Células Madin Darby de Rim Canino , Receptores Virais/metabolismo , Cultura de Vírus/métodos , Replicação Viral , Animais , Betacoronavirus , COVID-19 , Linhagem Celular , Galinhas/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Cães , Ovos , Humanos , Pandemias , Pneumonia Viral , SARS-CoV-2 , Síndrome Respiratória Aguda Grave
17.
Euro Surveill ; 25(47)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33243355

RESUMO

The coronavirus disease pandemic was declared in March 2020, as the southern hemisphere's winter approached. Australia expected co-circulation of severe acute respiratory syndrome coronavirus 2, influenza and other seasonal respiratory viruses. However, influenza notifications were 7,029 (March-September) compared with an average 149,832 for the same period in 2015-2019 [corrected], despite substantial testing. Restrictions on movement within and into Australia may have temporarily eliminated influenza. Other respiratory pathogens also showed remarkably changed activity in 2020.


Assuntos
Infecções por Coronavirus/epidemiologia , Notificação de Doenças/estatística & dados numéricos , Influenza Humana/epidemiologia , Infecções Respiratórias/epidemiologia , Austrália/epidemiologia , COVID-19 , Coronavirus , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pandemias , Vigilância da População , SARS-CoV-2 , Estações do Ano , Vigilância de Evento Sentinela
18.
Emerg Infect Dis ; 25(10): 1988-1991, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31310233

RESUMO

Active surveillance in high-risk sites in Cambodia has identified multiple low-pathogenicity influenza A(H7) viruses, mainly in ducks. None fall within the A/Anhui/1/2013(H7N9) lineage; however, some A(H7) viruses from 2018 show temporal and phylogenetic similarity to the H7N4 virus that caused a nonfatal infection in Jiangsu Province, China, in December 2017.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Patos/virologia , Vírus da Influenza A , Influenza Aviária/epidemiologia , Doenças das Aves Domésticas/epidemiologia , Animais , Camboja/epidemiologia , China/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Humanos , Vírus da Influenza A/genética , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Filogenia , Doenças das Aves Domésticas/virologia
19.
J Virol ; 92(4)2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29187546

RESUMO

Small-animal models have been used to obtain many insights regarding the pathogenesis and immune responses induced following infection with human respiratory syncytial virus (hRSV). Among those described to date, infections in cotton rats, mice, guinea pigs, chinchillas, and Syrian hamsters with hRSV strains Long and/or A2 have been well characterized, although clinical isolates have also been examined. Ferrets are also susceptible to hRSV infection, but the pathogenesis and immune responses elicited following infection have not been well characterized. Here, we describe the infection of adult ferrets with hRSV Long or A2 via the intranasal route and characterized virus replication, as well as cytokine induction, in the upper and lower airways. Virus replication and cytokine induction during the acute phase of infection (days 0 to 15 postinfection) were similar between the two strains, and both elicited high levels of F glycoprotein-specific binding and neutralizing antibodies following virus clearance (days 16 to 22 postinfection). Importantly, we demonstrate transmission from experimentally infected donor ferrets to cohoused naive recipients and have characterized virus replication and cytokine induction in the upper airways of infected contact animals. Together, these studies provide a direct comparison of the pathogenesis of hRSV Long and A2 in ferrets and highlight the potential of this animal model to study serological responses and examine interventions that limit transmission of hRSV.IMPORTANCE Ferrets have been widely used to study pathogenesis, immunity, and transmission following human influenza virus infections; however, far less is known regarding the utility of the ferret model to study hRSV infections. Following intranasal infection of adult ferrets with the well-characterized Long or A2 strain of hRSV, we report virus replication and cytokine induction in the upper and lower airways, as well as the development of virus-specific humoral responses. Importantly, we demonstrate transmission of hRSV from experimentally infected donor ferrets to cohoused naive recipients. Together, these findings significantly enhance our understanding of the utility of the ferret as a small-animal model to investigate aspects of hRSV pathogenesis and immunity.


Assuntos
Modelos Animais de Doenças , Imunidade Humoral/imunologia , Infecções por Vírus Respiratório Sincicial/transmissão , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/patogenicidade , Infecções Respiratórias/virologia , Animais , Furões , Células HeLa , Humanos , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/imunologia , Infecções Respiratórias/imunologia , Carga Viral , Replicação Viral
20.
J Virol ; 92(16)2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29875251

RESUMO

Global swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise.IMPORTANCE We describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016.


Assuntos
Variação Genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Suínos/virologia , Animais , Genótipo , Humanos , Vírus da Influenza A/genética , Epidemiologia Molecular , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Filogenia , Queensland/epidemiologia , Doenças dos Suínos/epidemiologia , Austrália Ocidental/epidemiologia
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