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1.
Int J Infect Dis ; 90: 84-96, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669593

RESUMO

BACKGROUND: This study compared the genomes of influenza viruses that caused mild infections among outpatients and severe infections among hospitalized patients in Singapore, and characterized their molecular evolution and receptor-binding specificity. METHODS: The complete genomes of influenza A/H1N1, A/H3N2 and B viruses that caused mild infections among outpatients and severe infections among inpatients in Singapore during 2012-2015 were sequenced and characterized. Using various bioinformatics approaches, we elucidated their evolutionary, mutational and structural patterns against the background of global and vaccine strains. RESULTS: The phylogenetic trees of the 8 gene segments revealed that the outpatient and inpatient strains overlapped with representative global and vaccine strains. We observed a cluster of inpatients with A/H3N2 strains that were closely related to vaccine strain A/Texas/50/2012(H3N2). Several protein sites could accurately discriminate between outpatient versus inpatient strains, with site 221 in neuraminidase (NA) achieving the highest accuracy for A/H3N2. Interestingly, amino acid residues of inpatient but not outpatient isolates at those sites generally matched the corresponding residues in vaccine strains, except at site 145 of hemagglutinin (HA). This would be especially relevant for future surveillance of A/H3N2 strains in relation to their antigenicity and virulence. Furthermore, we observed a trend in which the HA proteins of influenza A/H3N2 and A/H1N1 exhibited enhanced ability to bind both avian and human host cell receptors. In contrast, the binding ability to each receptor was relatively stable for the HA of influenza B. CONCLUSIONS: Overall, our findings extend our understanding of the molecular and structural evolution of influenza virus strains in Singapore within the global context of these dynamic viruses.


Assuntos
Evolução Molecular , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenzavirus B/genética , Adolescente , Adulto , Idoso , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Hospitalização , Humanos , Influenza Humana/virologia , Pessoa de Meia-Idade , Mutação , Neuraminidase/genética , Pacientes Ambulatoriais , Filogenia , Receptores Virais/química , Singapura , Proteínas Virais/genética , Adulto Jovem
2.
Biochemistry (Mosc) ; 84(10): 1177-1185, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694513

RESUMO

It was previously shown that hemagglutinin residues Thr155, Glu158, and Ser228 are crucial for the recognition of Neu5Gc. In this study, we demonstrated that the ability to bind the Neu5Gc-terminated receptor is related to the amino acid 145: viruses of years 1972-1999 with Lys145 bind to the receptor, whereas viruses with Asn145 do not. Sporadic appearance and disappearance of the ability to bind Neu5Gc oligosaccharides and the absence of Neu5Gc in the composition of human glycoconjugates indicate the non-adaptive nature of this ability. It was previously shown that unlike H1N1 viruses, H3N2 viruses of years 1968-1989 did not distinguish between Neu5Acα2-6Galß1-4Glc (6'SL) and Neu5Acα2-6Galß1-4GlcNAc (6'SLN). H3N2 viruses isolated after 1993 have acquired the ability to distinguish between 6'SL and 6'SLN, similarly to H1N1 viruses. We found that the affinity for 6'SLN has gradually increased from 1992 to 2003. After 2003, the viruses lost the ability to bind a number of sialosides, including 6'SL, that were good receptors for earlier H3N2 viruses, and retained high affinity for 6'SLN only, which correlated with the acquisition of new glycosylation sites at positions 122, 133, and 144, as well as Glu190Asp and Gly225Asp substitutions, in hemagglutinin. These substitutions are also responsible for the receptor-binding phenotype of human H1N1 viruses. We conclude that the convergent evolution of the receptor specificity of the H1N1 and H3N2 viruses indicates that 6'SLN is the optimal natural human receptor for influenza viruses.


Assuntos
Vírus da Influenza A Subtipo H3N2/química , Receptores Virais/química , Sítios de Ligação , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/metabolismo , Receptores Virais/sangue
3.
Vet Res ; 50(1): 77, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590684

RESUMO

This report describes the detection of a triple reassortant swine influenza A virus of H1avN2 subtype. It evolved from an avian-like swine H1avN1 that first acquired the N2 segment from a seasonal H3N2, then the M segment from a 2009 pandemic H1N1, in two reassortments estimated to have occurred 10 years apart. This study illustrates how recurrent influenza infections increase the co-infection risk and facilitate evolutionary jumps by successive gene exchanges. It recalls the importance of appropriate biosecurity measures inside holdings to limit virus persistence and interspecies transmissions, which both contribute to the emergence of new potentially zoonotic viruses.


Assuntos
Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H1N2/fisiologia , Vírus da Influenza A Subtipo H3N2/fisiologia , Vírus Reordenados/fisiologia , Doenças dos Suínos/virologia , Animais , França , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N2/genética , Vírus da Influenza A Subtipo H3N2/genética , Sus scrofa , Suínos
4.
MMWR Morb Mortal Wkly Rep ; 68(40): 880-884, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31600182

RESUMO

During May 19-September 28, 2019,* low levels of influenza activity were reported in the United States, with cocirculation of influenza A and influenza B viruses. In the Southern Hemisphere seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries. In late September, the World Health Organization (WHO) recommended components for the 2020 Southern Hemisphere influenza vaccine and included an update to the A(H3N2) and B/Victoria-lineage components. Annual influenza vaccination is the best means for preventing influenza illness and its complications, and vaccination before influenza activity increases is optimal. Health care providers should recommend vaccination for all persons aged ≥6 months who do not have contraindications to vaccination (1).


Assuntos
Saúde Global/estatística & dados numéricos , Vacinas contra Influenza/química , Influenza Humana/epidemiologia , Vigilância da População , Farmacorresistência Viral , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/efeitos dos fármacos , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Influenza Humana/virologia , Estações do Ano , Estados Unidos/epidemiologia
5.
Emerg Microbes Infect ; 8(1): 1280-1290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31495283

RESUMO

The H3N2 influenza viruses became widespread in humans during the 1968 H3N2 pandemic and have been a major cause of influenza epidemics ever since. Different lineages of H3N2 influenza viruses are also commonly found in animals. If a different lineage of H3N2 virus jumps to humans, a human influenza pandemic could occur with devastating consequences. Here, we studied the genetics, receptor-binding properties, and replication and transmission in mammals of 15 H3N2 avian influenza viruses detected in live poultry markets in China. We found that the H3N2 avian influenza viruses are complicated reassortants with distinct replication phenotypes in mice. Five viruses replicated efficiently in mice and bound to both human-type and avian-type receptors. These viruses transmitted efficiently to direct-contact guinea pigs, and three of them also transmitted among guinea pigs and ferrets via respiratory droplets. Moreover, ferret antiserum induced by human H3N2 viruses did not react with any of the H3N2 avian influenza viruses. Our study demonstrates that the H3N2 avian influenza viruses pose a clear threat to human health and emphasizes the need for continued surveillance and evaluation of the H3N2 influenza viruses circulating in nature.


Assuntos
Transmissão de Doença Infecciosa , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/fisiologia , Influenza Aviária/virologia , Aves Domésticas/virologia , Ligação Viral , Animais , China , Modelos Animais de Doenças , Furões , Cobaias , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Camundongos Endogâmicos BALB C , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/fisiologia , Receptores Virais/metabolismo , Doenças dos Roedores/virologia , Replicação Viral
6.
BMC Infect Dis ; 19(1): 676, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370782

RESUMO

BACKGROUND: In addition to seasonal influenza viruses recently circulating in humans, avian influenza viruses (AIVs) of H5N1, H5N6 and H7N9 subtypes have also emerged and demonstrated human infection abilities with high mortality rates. Although influenza viral infections are usually diagnosed using viral isolation and serological/molecular analyses, the cost, accessibility, and availability of these methods may limit their utility in various settings. The objective of this study was to develop and optimized a multiplex detection system for most influenza viruses currently infecting humans. METHODS: We developed and optimized a multiplex detection system for most influenza viruses currently infecting humans including two type B (both Victoria lineages and Yamagata lineages), H1N1, H3N2, H5N1, H5N6, and H7N9 using Reverse Transcriptional Loop-mediated Isothermal Amplification (RT-LAMP) technology coupled with a one-pot colorimetric visualization system to facilitate direct determination of results without additional steps. We also evaluated this multiplex RT-LAMP for clinical use using a total of 135 clinical and spiked samples (91 influenza viruses and 44 other human infectious viruses). RESULTS: We achieved rapid detection of seasonal influenza viruses (H1N1, H3N2, and Type B) and avian influenza viruses (H5N1, H5N6, H5N8 and H7N9) within an hour. The assay could detect influenza viruses with high sensitivity (i.e., from 100 to 0.1 viral genome copies), comparable to conventional RT-PCR-based approaches which would typically take several hours and require expensive equipment. This assay was capable of specifically detecting each influenza virus (Type B, H1N1, H3N2, H5N1, H5N6, H5N8 and H7N9) without cross-reactivity with other subtypes of AIVs or other human infectious viruses. Furthermore, 91 clinical and spiked samples confirmed by qRT-PCR were also detected by this multiplex RT-LAMP with 98.9% agreement. It was more sensitive than one-step RT-PCR approach (92.3%). CONCLUSIONS: Results of this study suggest that our multiplex RT-LAMP assay may provide a rapid, sensitive, cost-effective, and reliable diagnostic method for identifying recent influenza viruses infecting humans, especially in locations without access to large platforms or sophisticated equipment.


Assuntos
Colorimetria/métodos , Vírus da Influenza A/genética , Influenza Humana/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Reações Cruzadas , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Virus da Influenza A Subtipo H5N1/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/patogenicidade , Transcrição Reversa
7.
Nat Commun ; 10(1): 3526, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387995

RESUMO

Segmentation of viral genomes into multiple RNAs creates the potential for replication of incomplete viral genomes (IVGs). Here we use a single-cell approach to quantify influenza A virus IVGs and examine their fitness implications. We find that each segment of influenza A/Panama/2007/99 (H3N2) virus has a 58% probability of being replicated in a cell infected with a single virion. Theoretical methods predict that IVGs carry high costs in a well-mixed system, as 3.6 virions are required for replication of a full genome. Spatial structure is predicted to mitigate these costs, however, and experimental manipulations of spatial structure indicate that local spread facilitates complementation. A virus entirely dependent on co-infection was used to assess relevance of IVGs in vivo. This virus grows robustly in guinea pigs, but is less infectious and does not transmit. Thus, co-infection allows IVGs to contribute to within-host spread, but complete genomes may be critical for transmission.


Assuntos
Vírus Defeituosos/patogenicidade , Genoma Viral , Vírus da Influenza A Subtipo H3N2/patogenicidade , Influenza Humana/transmissão , Replicação Viral/genética , Animais , Vírus Defeituosos/genética , Modelos Animais de Doenças , Cães , Evolução Molecular , Feminino , Cobaias , Células HEK293 , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/virologia , Funções Verossimilhança , Células Madin Darby de Rim Canino , Modelos Biológicos , RNA Viral/genética , Análise de Célula Única , Carga Viral , Vírion/genética , Eliminação de Partículas Virais/genética
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(8): 840-842, 2019 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-31378046

RESUMO

In this study, the swabs were collected among patients with an influenza-like illness (ILI) admitted to 2 sentinel surveillance hospitals of Yantai from April 2014 to August 2017. All specimen were cultured and identified by hemagglutination inhibition assay. Complete sequences of Hemagglutinin (HA) of influenza A were amplified, sequenced and analyzed using molecular and phylogenetic methods. The potential vaccine efficacy were calculated using Pepitope model. The results showed that the antigenicity of A (H3N2) had changed greatly. 8 strains of influenza A (H1N1) pdm09 belonged to subclade 6B.1 and 14 strains clustered in 6B.2. 12 strains of influenza A (H3N2) fell into subgroup 3C.3a and 33 strains clustered in 3C.2a. Several residues at antigen sites and potential glycosylation sites had changed in influenza A strains. Vaccine efficacy of influenza A (H1N1) pdm09 in 2015/2016 and 2016/2017 seasons were 77.29% and 79.11% of that of a perfect match with vaccine strain, meanwhile vaccine efficacy of influenza A (H3N2) in 2014/2015, 2015/2016 and 2016/2017 were-5.18%, 16.97% and 42.05% separately. In conclusion, the influenza A virus circulated in Yantai from 2014 to 2017 presented continual genetic variation. The recommended vaccine strains still afforded protection against influenza A (H1N1) pdm09 strains and provided suboptimal protection against influenza A (H3N2) strains.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Potência de Vacina , China , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Humanos , Filogenia , RNA Viral
9.
Emerg Microbes Infect ; 8(1): 1157-1167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31373538

RESUMO

The spread of influenza A/H3N2 variants possessing the hemagglutinin 121 K mutation and the unexpectedly high incidence of influenza in the 2017-2018 northern hemisphere influenza season have raised serious concerns about the next pandemic. We summarized the national surveillance data of seasonal influenza in China and identified marked differences in influenza epidemics between northern and southern China, particularly the predominating subtype and the presence of an additional summer peak in southern China. Notably, a minor spring peak of influenza caused by a different virus subtype was also observed. We also revealed that the 3C.2a lineage was dominant from the summer of 2015 to the end of the 2015-2016 peak season in China, after which the 3C.2a2 lineage predominated despite the importation and co-circulation of the 121 K variants of 3C.2a1 and 3C.2a3 lineages at the global level. Finally, an analysis based on genetic distances revealed a delay in A/H3N2 vaccine strain update. Overall, our results highlight the complicated circulation pattern of seasonal influenza in China and the necessity for a timely vaccine strain update worldwide.


Assuntos
Variação Genética , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , China/epidemiologia , Humanos , Incidência , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Epidemiologia Molecular , Filogeografia
10.
Dokl Biochem Biophys ; 486(1): 201-205, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367821

RESUMO

Infection of mice with influenza A viruses led to the formation of clones of lymphocytes that specifically recognizes viral domains in the central zone of the NSP protein (amino acid positions 83-119). Computer analysis of the primary structure of the NSP protein showed the presence of T-cell epitopes in the central part of the NSP molecule. The findings indicate that the viral NSP gene is expressed in the infected animals and verify the concept of the bipolar strategy (ambisense strategy) of the influenza A virus genome.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/fisiologia , Leucócitos/imunologia , RNA Viral/genética , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , Leucócitos/virologia , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos , Proteínas Virais/química , Proteínas Virais/metabolismo
11.
Indian J Med Microbiol ; 37(1): 42-49, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424009

RESUMO

Introduction: Influenza A(H1N1)pdm09 virus, since its identification in April 2009, has continued to cause significant outbreaks of respiratory tract infections including pandemics in humans. In the course of its evolution, the virus has acquired many mutations with an ability to cause increased disease severity. A regular molecular surveillance of the virus is essential to mark the evolutionary changes that may cause a shift to the viral behavior. Materials and Methods: Samples of Throat/Nasal swabs were collected from a total of 3715 influenza-like illness cases and screened by Real-time Reverse Transcription-Polymerase Chain Reaction for influenza viruses. Nucleotide sequence analysis was done to identify changes in antigenicity of the virus strains. Results: The present study describes the molecular characteristics of influenza A(H1N1)pdm09 viruses detected in Assam of Northeast India during 2009-2015. Influenza A viruses were detected in 11.4% (425/3715), of which influenza A(H1N1)pdm09 viruses were detected in 41.4% (176/425). The nucleotide sequencing of influenza A(H1N1)pdm09 viruses revealed a total of 17 and 22 amino acid substitutions in haemagglutinin (HA) and neuraminidase (NA) genes of the virus, respectively, compared to contemporary vaccine strain A/California/07/2009. The important mutations detected in HA genes of A/Assam(H1N1)pdm09 strains included E391K, K180Q and S202T. Mutation 'N248D' which has an ability to develop oseltamivir resistance was also detected in NA gene of A/Assam(H1N1)pdm09 strains. Conclusions: Regular molecular surveillance of influenza A(H1N1)pdm09 is important to monitor the viral behavior in terms of increase virulence, drug resistance pattern and emergence of novel strains.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/epidemiologia , Neuraminidase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/farmacologia , Sequência de Bases , Criança , Pré-Escolar , Feminino , Variação Genética/genética , Humanos , Índia/epidemiologia , Lactente , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Oseltamivir/farmacologia , Filogenia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Adulto Jovem
12.
Emerg Microbes Infect ; 8(1): 1017-1026, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31287780

RESUMO

Host switch events of influenza A viruses (IAVs) continuously pose a zoonotic threat to humans. In 2013, swine-origin H1N1 IAVs emerged in dogs soon after they were detected in swine in the Guangxi province of China. This host switch was followed by multiple reassortment events between these H1N1 and previously circulating H3N2 canine IAVs (IAVs-C) in dogs. To evaluate the phenotype of these newly identified viruses, we characterized three swine-origin H1N1 IAVs-C and one reassortant H1N1 IAV-C. We found that H1N1 IAVs-C predominantly bound to human-type receptors, efficiently transmitted via direct contact in guinea pigs and replicated in human lung cells. Moreover, the swine-origin H1N1 IAVs-C were lethal in mice and were transmissible by respiratory droplets in guinea pigs. Importantly, sporadic human infections with these viruses have been detected, and preexisting immunity in humans might not be sufficient to prevent infections with these new viruses. Our results show the potential of H1N1 IAVs-C to infect and transmit in humans, suggesting that these viruses should be closely monitored in the future.


Assuntos
Doenças do Cão/virologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Animais , China , Doenças do Cão/mortalidade , Cães , Feminino , Cobaias , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/mortalidade , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/virologia , Vírus Reordenados/classificação , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/patogenicidade , Suínos , Doenças dos Suínos/mortalidade , Virulência
13.
PLoS One ; 14(7): e0217607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31323023

RESUMO

Southern China is considered an important source of influenza virus pandemics because of the large, diverse viral reservoirs in poultry and swine. To examine the trend in influenza A virus of swine (IAV-S), an active surveillance program has been conducted from 2013 to 2015 in Guangdong, China. The phylogenetic analyses showed that the external genes of the isolates were assigned to the Eurasian avian-like swine (EA) H1N1 and/or human-like H3N2 lineages with multiple substitutions, indicating a notable genetic shift. Moreover, the internal genes derived from different origins (PB2, PB1, PA, NP: pdm/09 (pandemic influenza virus 2009)-origin, M: pdm/09- or EA-origin, NS: North American Triple Reassortant (TR)-origin have become the dominant backbone of IAV-S in southern China. According to the origins of the eight gene segments, the isolates can be categorized into five genotypes. The results of mice experiment showed that the YJ4 (genotype 1) and DG2 (genotype 4) are the most pathogenic to mice, and the viruses are observed in kidneys and brains, indicating the systemic infection. The alterations of the IAV-S gene composition supported the continued implementation of the intensive surveillance of IAV-S and the greater attention focused on potential shifts toward transmission to humans.


Assuntos
Evolução Molecular , Genótipo , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Infecções por Orthomyxoviridae/genética , Doenças dos Suínos/genética , Animais , China , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/veterinária , Suínos , Doenças dos Suínos/transmissão , Doenças dos Suínos/virologia
14.
Nat Commun ; 10(1): 3338, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350391

RESUMO

Several vaccines are approved in the United States for seasonal influenza vaccination every year. Here we compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. Fold change in HI and antibody binding to HA1 trends higher for H1N1pdm09 and H3N2 but not against B strains in groups vaccinated with FluBlok compared with FluCelvax and Fluzone. Antibody-affinity maturation occurs against HA1 domain of H1N1pdm09, H3N2 and B following vaccination with all vaccine platforms, but not against H1N1pdm09-HA2. Importantly, prior year vaccination of subjects receiving repeat vaccinations demonstrated reduced antibody-affinity maturation to HA1 of all three influenza virus strains irrespective of the vaccine platform. This study identifies an important impact of repeat vaccination on antibody-affinity maturation following vaccination, which may contribute to lower vaccine effectiveness of seasonal influenza vaccines in humans.


Assuntos
Afinidade de Anticorpos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Criança , Pré-Escolar , Feminino , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
15.
MMWR Morb Mortal Wkly Rep ; 68(24): 544-551, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31220057

RESUMO

Influenza activity* in the United States during the 2018-19 season (September 30, 2018-May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)† activity began increasing in November, peaked during mid-February, and returned to below baseline in mid-April; the season lasted 21 weeks,§ making it the longest season in 10 years. Illness attributed to influenza A viruses predominated, with very little influenza B activity. Two waves of influenza A were notable during this extended season: influenza A(H1N1)pdm09 viruses from October 2018 to mid-February 2019 and influenza A(H3N2) viruses from February through May 2019. Compared with the 2017-18 influenza season, rates of hospitalization this season were lower for adults, but were similar for children. Although influenza activity is currently below surveillance baselines, testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Vigilância da População , Adolescente , Adulto , Idoso , Antivirais/farmacologia , Criança , Mortalidade da Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Farmacorresistência Viral , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza B/efeitos dos fármacos , Vírus da Influenza B/genética , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/química , Influenza Humana/mortalidade , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Pneumonia/mortalidade , Estações do Ano , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , Adulto Jovem
16.
Virol Sin ; 34(5): 583-591, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240620

RESUMO

Conventional influenza vaccines need to be designed and manufactured yearly. However, they occasionally provide poor protection owing to antigenic mismatch. Hence, there is an urgent need to develop universal vaccines against influenza virus. Using nucleoprotein (NP) and extracellular domain of matrix protein 2 (M2e) genes from the influenza A virus A/Beijing/30/95 (H3N2), we constructed four recombinant vaccinia virus-based influenza vaccines carrying NP fused with one or four copies of M2e genes in different orders. The recombinant vaccinia viruses were used to immunize BALB/C mice. Humoral and cellular responses were measured, and then the immunized mice were challenged with the influenza A virus A/Puerto Rico/8/34 (PR8). NP-specific humoral response was elicited in mice immunized with recombinant vaccinia viruses carrying full-length NP, while robust M2e-specific humoral response was elicited only in the mice immunized with recombinant vaccinia viruses carrying multiple copies of M2e. All recombinant viruses elicited NP- and M2e-specific cellular immune responses in mice. Only immunization with RVJ-4M2eNP induced remarkably higher levels of IL-2 and IL-10 cytokines specific to M2e. Furthermore, RVJ-4M2eNP immunization provided the highest cross-protection in mice challenged with 20 MLD50 of PR8. Therefore, the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP, which expresses a fusion antigen of full-length NP preceded by four M2e repeats. These results suggest that the rational fusion of NP and multiple M2e antigens is critical toward inducing protective immune responses, and the 4M2eNP fusion antigen may be employed to develop a universal influenza vaccine.


Assuntos
Proteção Cruzada , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Nucleoproteínas/imunologia , Vaccinia/genética , Proteínas da Matriz Viral/imunologia , Animais , Anticorpos Antivirais/sangue , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização , Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/genética , Camundongos Endogâmicos BALB C , Nucleoproteínas/genética , Infecções por Orthomyxoviridae/prevenção & controle , Organismos Livres de Patógenos Específicos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Proteínas da Matriz Viral/genética
17.
PLoS Pathog ; 15(6): e1007860, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31181126

RESUMO

Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2nd sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein.


Assuntos
Vírus da Influenza A Subtipo H2N2 , Vírus da Influenza A Subtipo H3N2 , Neuraminidase , Receptores Virais , Proteínas Virais , Vírion , Animais , Sítios de Ligação , Cães , Humanos , Vírus da Influenza A Subtipo H2N2/química , Vírus da Influenza A Subtipo H2N2/genética , Vírus da Influenza A Subtipo H2N2/metabolismo , Vírus da Influenza A Subtipo H3N2/química , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/metabolismo , Células Madin Darby de Rim Canino , Ácido N-Acetilneuramínico/genética , Ácido N-Acetilneuramínico/metabolismo , Neuraminidase/química , Neuraminidase/genética , Neuraminidase/metabolismo , Receptores Virais/química , Receptores Virais/genética , Receptores Virais/metabolismo , Células Vero , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo , Vírion/química , Vírion/genética , Vírion/metabolismo
18.
Cell Host Microbe ; 25(6): 836-844.e5, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31151913

RESUMO

Egg-based seasonal influenza vaccines are the major preventive countermeasure against influenza virus. However, their effectiveness can be compromised when antigenic changes arise from egg-adaptive mutations on influenza hemagglutinin (HA). The L194P mutation is commonly observed in egg-based H3N2 vaccine seed strains and significantly alters HA antigenicity. An approach to prevent L194P would therefore be beneficial. We show that emergence of L194P during egg passaging can be impeded by preexistence of a G186V mutation, revealing strong incompatibility between these mutations. X-ray structures illustrate that individual G186V and L194P mutations have opposing effects on the HA receptor-binding site (RBS), and when both G186V and L194P are present, the RBS is severely disrupted. Importantly, wild-type HA antigenicity is maintained with G186V, but not L194P. Our results demonstrate that these epistatic interactions can be used to prevent the emergence of mutations that adversely alter antigenicity during egg adaptation.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H3N2/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Mutação de Sentido Incorreto , Adaptação Biológica , Animais , Antígenos Virais/química , Antígenos Virais/genética , Antígenos Virais/imunologia , Sítios de Ligação , Embrião de Galinha , Cristalografia por Raios X , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Vírus da Influenza A Subtipo H3N2/genética , Conformação Proteica , Tecnologia Farmacêutica/métodos , Cultura de Vírus/métodos
19.
Cell Host Microbe ; 25(6): 827-835.e6, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31104946

RESUMO

Viral glycoproteins are under constant immune surveillance by a host's adaptive immune responses. Antigenic variation including glycan introduction or removal is among the mechanisms viruses have evolved to escape host immunity. Understanding how glycosylation affects immunodominance on complex protein antigens may help decipher underlying B cell biology. To determine how B cell responses can be altered by such modifications, we engineered glycans onto the influenza virus hemagglutinin (HA) and characterized the molecular features of the elicited humoral immunity in mice. We found that glycan addition changed the initially diverse antibody repertoire into an epitope-focused, genetically restricted response. Structural analyses showed that one antibody gene family targeted a previously subdominant, occluded epitope at the head interface. Passive transfer of this antibody conferred Fc-dependent protection to influenza virus-challenged mice. These results have potential implications for next-generation viral vaccines aimed at directing B cell responses to preferred epitope(s).


Assuntos
Anticorpos Antivirais/imunologia , Epitopos/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Polissacarídeos/metabolismo , Animais , Anticorpos Antivirais/metabolismo , Cristalografia por Raios X , Epitopos/química , Epitopos/genética , Epitopos/metabolismo , Glicosilação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Imunização Passiva , Vírus da Influenza A Subtipo H3N2/genética , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle , Ligação Proteica , Conformação Proteica , Análise de Sobrevida
20.
J Coll Physicians Surg Pak ; 29(5): 459-462, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31036119

RESUMO

OBJECTIVE: To determine the frequency of infections caused by Influenza viruses, i.e. Influenza A (H1N1) pdm09, Influenza A (H3N2) and Influenza B in patients presenting with respiratory tract infections, i.e. influenza-like illness (ILI) and severe acute respiratory illness (SARI). STUDY DESIGN: Descriptive, cross-sectional study. PLACE AND DURATION OF STUDY: Department of Virology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from October 2017 to February 2018. METHODOLOGY: A total of 624 samples from patients with respiratory tract infections (both ILI and SARI) were included in the study. Specimens collected from the patients included nasal swabs and throat swabs, which were transported in viral transport medium (VTM) to Virology Department, AFIP. Multiplex PCR was done for Influenza A (H1N1) pdm09, Influenza A (H3N2) and Influenza B. RESULTS: A total of 200 (32%) samples were found to be positive for Influenza viruses. Out of total 624 samples analysed, 220 (35.3%) were from females and 404 (64.7%) from males. Among these, 510 (81.7%) presented with ILI and 114 (18.3%) with SARI. Among positive samples, 120 (19.2%) samples were positive for H1N1, 61 (9.8%) for H3N2 and 19 (3%) were positive for Influenza B. Highest number of positive cases occurred in the month of January, i.e. 148 (74%) cases. Only 3 (2.5%) patients out of 120 infected with H1N1 were in age group-I (0-5 years). While in age group-II (6-30 years), age group-III (31-60 years), and age group-IV (>60 years); 39 (32.5%), 63 (52.5%) and 15 (12.5%) patients were infected by H1N1, respectively. Maximum patients with H3N2 infection were in age group-III; 30 (49.2%) of the total 61. Commonest Influenza subtype in age group-IV was H3N2 found in 20 (32.8%) patients, followed by H1N1 in 15 (12.5%) patients. CONCLUSION: The dominant subtype in our set-up, during winter of 2017-2018, was Influenza A (H1N1) pdm09. Highest numbers of positive cases were recorded in the month of January. People with ILI and SARI should be tested for Influenza viruses to avoid unnecessary use of antibiotics.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções Respiratórias/diagnóstico , Síndrome Respiratória Aguda Grave/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estações do Ano , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/virologia , Adulto Jovem
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