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1.
J Gen Virol ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424377

RESUMO

Long-term culture of the human lung adenocarcinoma cell line A549 promotes the differentiation of these cells toward an alveolar type II cell phenotype. Here, we evaluated the susceptibility of long-term cultured A549 cells to human influenza viruses. A549 cells were cultured continuously for 25 days (D25-A549) or 1 day (D1-A549) in Ham's F12K medium. Six human influenza A viruses grew much faster in D25-A549 cells than in D1-A549 cells; however, two influenza B viruses replicated poorly in both cell types. Two avian influenza viruses replicated efficiently in both cell types, with similar titres. Expression levels of human virus receptors were higher in D25-A549 cells than in D1-A549 cells. D25-A549 cells thus more efficiently support the replication of human influenza A viruses compared with D1-A549 cells. Our data suggest that long-term cultured A549 cells will be useful for influenza A virus research.

2.
Antiviral Res ; 171: 104591, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31421167

RESUMO

Clarithromycin (CAM), a 14-membered ring macrolide, has anti-inflammatory and immunomodulatory actions and antiviral effects in seasonal influenza virus infection. We examined the prophylactic and therapeutic efficacy of CAM against H5N1 highly pathogenic and H7N9 low pathogenic avian influenza virus infections in cynomolgus monkeys. CAM suppressed H5N1 virus-induced severe signs of disease in the treated monkeys and inhibited virus propagation in tracheal samples and the production of inflammatory cytokines in the lungs of monkeys infected with H5N1 and H7N9 viruses. The prophylactic administration of CAM showed more suppressive effects on clinical signs of disease and viral titers than did therapeutic administration. Thus, since administration of CAM alone showed a tendency to ameliorate clinical sings and to reduce levels of inflammatory cytokines, the macrolides are expected to have effects in combination with the other antiviral drugs on the prophylactic and treatment of patients with severe avian influenza virus infection, which should be further investigated.

3.
PLoS Negl Trop Dis ; 13(8): e0007654, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31369554

RESUMO

The 2013-2016 Ebola virus outbreak in West Africa was the largest and deadliest outbreak to date. Here we conducted a serological study to examine the antibody levels in survivors and the seroconversion in close contacts who took care of Ebola-infected individuals, but did not develop symptoms of Ebola virus disease. In March 2017, we collected blood samples from 481 individuals in Makeni, Sierra Leone: 214 survivors and 267 close contacts. Using commercial, quantitative ELISAs, we tested the plasma for IgG-specific antibodies against three major viral antigens: GP, the only viral glycoprotein expressed on the virus surface; NP, the most abundant viral protein; and VP40, a major structural protein of Zaire ebolavirus. We also determined neutralizing antibody titers. In the cohort of Ebola survivors, 97.7% of samples (209/214) had measurable antibody levels against GP, NP, and/or VP40. Of these positive samples, all but one had measurable neutralizing antibody titers against Ebola virus. For the close contacts, up to 12.7% (34/267) may have experienced a subclinical virus infection as indicated by detectable antibodies against GP. Further investigation is warranted to determine whether these close contacts truly experienced subclinical infections and whether these asymptomatic infections played a role in the dynamics of transmission.

4.
J Immunol ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399519

RESUMO

Avian influenza vaccines exhibit poor immunogenicity in humans. We hypothesized that one factor underlying weak B cell responses was sequence divergence between avian and seasonal influenza hemagglutinin proteins, thus limiting the availability of adequate CD4 T cell help. To test this, a novel chimeric hemagglutinin protein (cH7/3) was derived, comprised of the stem domain from seasonal H3 hemagglutinin and the head domain from avian H7. Immunological memory to seasonal influenza was established in mice, through strategies that included seasonal inactivated vaccines, Flumist, and synthetic peptides derived from the H3 stalk domain. After establishment of memory, mice were vaccinated with H7 or cH7/3 protein. The cH7/3 Ag was able to recall H3-specific CD4 T cells, and this potentiated CD4 T cell response was associated with enhanced early germinal center response and rapid elicitation of Abs to H7, including Abs specific for the H7 head domain. These results suggest that in pandemic situations, inclusion of CD4 T cell epitopes from seasonal viruses have the potential to overcome the poor immunogenicity of avian vaccines by helping B cells and conferring greater subtype-specific Ab response to viral HA.

5.
Vaccine ; 37(35): 5051-5058, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31300285

RESUMO

Avian influenza virus (AIV) is an extraordinarily diverse pathogen that causes significant morbidity in domesticated poultry populations and threatens human life with looming pandemic potential. Controlling avian influenza in susceptible populations requires highly effective, economical and broadly reactive vaccines. Several AIV vaccines have proven insufficient despite their wide use, and better technologies are needed to improve their immunogenicity and broaden effectiveness. Previously, we developed a "mosaic" H5 subtype hemagglutinin (HA) AIV vaccine and demonstrated its broad protection against diverse highly pathogenic H5N1 and seasonal H1N1 virus strains in mouse and non-human primate models. There is a significant interest in developing effective and safe vaccines against AIV that cannot contribute to the emergence of new strains of the virus once circulating in poultry. Here, we report on the development of an H5 mosaic (H5M) vaccine antigen formulated with polyanhydride nanoparticles (PAN) that provide sustained release of encapsulated antigens. H5M vaccine constructs were immunogenic whether delivered by the modified virus Ankara (MVA) strain or encapsulated within PAN. Both humoral and cellular immune responses were generated in both specific-pathogen free (SPF) and commercial chicks. Importantly, chicks vaccinated by H5M constructs were protected in terms of viral shedding from divergent challenge with a low pathogenicity avian influenza (LPAI) strain at 8 weeks post-vaccination. In addition, protective levels of humoral immunity were generated against highly pathogenic avian influenza (HPAI) of the similar H5N1 and genetically dissimilar H5N2 viruses. Overall, the developed platform technologies (MVA vector and PAN encapsulation) were safe and provided high levels of sustained protection against AIV in chickens. Such approaches could be used to design more efficacious vaccines against other important poultry infections.

6.
Vaccine ; 37(32): 4533-4542, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31280945

RESUMO

Both influenza A and B viruses cause outbreaks of seasonal influenza resulting in significant morbidity and mortality. There are two antigenically distinct lineages of influenza B virus, Yamagata lineage (YL) and Victoria lineage (VL). Since both B lineages have been co-circulating for years, more than 70% of influenza vaccines currently manufactured are quadrivalent consisting of influenza A (H1N1), influenza A (H3N2), influenza B (YL) and influenza B (VL) antigens. Although quadrivalent influenza vaccines tend to elevate immunity to both influenza B lineages, estimated overall vaccine efficacy against influenza B is still only around 42%. Thus, a more effective influenza B vaccine is needed. To meet this need, we generated BM2-deficient, single-replication (BM2SR) influenza B vaccine viruses that encode surface antigens from influenza B/Wisconsin/01/2010 (B/WI01, YL) and B/Brisbane/60/2008 (B/Bris60, VL) viruses. The BM2SR-WI01 and BM2SR-Bris60 vaccine viruses are replication-deficient in vitro and in vivo, and can only replicate in a cell line that expresses the complementing BM2 protein. Both BM2SR viruses were non-pathogenic to mice, and vaccinated animals showed elevated mucosal and serum antibody responses to both Yamagata and Victoria lineages in addition to cellular responses. Serum antibody responses included lineage-specific hemagglutinin inhibition antibody (HAI) responses as well as responses to the stem region of the hemagglutinin (HA). BM2SR vaccine viruses provided apparent sterilizing immunity to mice against intra- and inter-lineage drifted B virus challenge. The data presented here support the feasibility of BM2SR as a platform for next-generation trivalent influenza vaccine development.

7.
MBio ; 10(3)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31213560

RESUMO

Avian influenza viruses (AIVs) must acquire mammalian-adaptive mutations before they can efficiently replicate in and transmit among humans. The PB2 E627K mutation is known to play a prominent role in the mammalian adaptation of AIVs. The H7N9 AIVs that emerged in 2013 in China easily acquired the PB2 E627K mutation upon replication in humans. Here, we generate a series of reassortant or mutant H7N9 AIVs and test them in mice. We show that the low polymerase activity attributed to the viral PA protein is the intrinsic driving force behind the emergence of PB2 E627K during H7N9 AIV replication in mice. Four residues in the N-terminal region of PA are critical in mediating the PB2 E627K acquisition. Notably, due to the identity of viral PA protein, the polymerase activity and growth of H7N9 AIV are highly sensitive to changes in expression levels of human ANP32A protein. Furthermore, the impaired viral polymerase activity of H7N9 AIV caused by the depletion of ANP32A led to reduced virus replication in Anp32a-/- mice, abolishing the acquisition of the PB2 E627K mutation and instead driving the virus to acquire the alternative PB2 D701N mutation. Taken together, our findings show that the emergence of the PB2 E627K mutation of H7N9 AIV is driven by the intrinsic low polymerase activity conferred by the viral PA protein, which also involves the engagement of mammalian ANP32A.IMPORTANCE The emergence of the PB2 E627K substitution is critical in the mammalian adaptation and pathogenesis of AIV. H7N9 AIVs that emerged in 2013 possess a prominent ability in gaining the PB2 E627K mutation in humans. Here, we demonstrate that the acquisition of the H7N9 PB2 E627K mutation is driven by the low polymerase activity conferred by the viral PA protein in human cells, and four PA residues are collectively involved in this process. Notably, the H7N9 PA protein leads to significant dependence of viral polymerase function on human ANP32A protein, and Anp32a knockout abolishes PB2 E627K acquisition in mice. These findings reveal that viral PA and host ANP32A are crucial for the emergence of PB2 E627K during adaptation of H7N9 AIVs to humans.

8.
Arch Virol ; 164(9): 2355-2358, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31227892

RESUMO

Equine influenza virus is an important pathogen for the horse industry because of its economic impact, and vaccination is a key control measure. Our previous work suggested that a mutation at position 144 in the hemagglutinin of Florida sublineage clade 2 viruses reduces the cross-neutralizing activity of antiserum against a former vaccine strain. To confirm this suggestion, here, we generated viruses by reverse genetics. Antibody titers against the mutated viruses were one-tenth to one-sixteenth of those against the former vaccine strain. Our findings confirm that this single amino acid substitution reduces the cross-reactivity of antiserum against this former Japanese vaccine.


Assuntos
Anticorpos Antivirais/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Doenças dos Cavalos/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/veterinária , Substituição de Aminoácidos , Animais , Reações Cruzadas , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Doenças dos Cavalos/virologia , Cavalos , Soros Imunes/imunologia , Vírus da Influenza A/genética , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/química , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia
9.
Cell ; 177(6): 1566-1582.e17, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31104840

RESUMO

Ebola virus (EBOV) remains a public health threat. We performed a longitudinal study of B cell responses to EBOV in four survivors of the 2014 West African outbreak. Infection induced lasting EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive B cells that subsequently underwent hypermutation. We characterized a large panel of EBOV glycoprotein-specific monoclonal antibodies (mAbs). Only a small subset of mAbs that bound glycoprotein by ELISA recognized cell-surface glycoprotein. However, this subset contained all neutralizing mAbs. Several mAbs protected against EBOV disease in animals, including one mAb that targeted an epitope under evolutionary selection during the 2014 outbreak. Convergent antibody evolution was seen across multiple donors, particularly among VH3-13 neutralizing antibodies specific for the GP1 core. Our study provides a benchmark for assessing EBOV vaccine-induced immunity.

10.
Nat Microbiol ; 4(8): 1268-1273, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31036910

RESUMO

Here, we developed hCK, a Madin-Darby canine kidney (MDCK) cell line that expresses high levels of human influenza virus receptors and low levels of avian virus receptors. hCK cells supported human A/H3N2 influenza virus isolation and growth much more effectively than conventional MDCK or human virus receptor-overexpressing (AX4) cells. A/H3N2 viruses propagated in hCK cells also maintained higher genetic stability than those propagated in MDCK and AX4 cells.

11.
Viruses ; 11(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987023

RESUMO

Highly pathogenic avian H5 influenza viruses persist among poultry and wild birds throughout the world. They sometimes cause interspecies transmission between avian and mammalian hosts. H5 viruses possessing the HA of subclade 2.3.4.4, 2.3.2.1, 2.2.1, or 7.2 were detected between 2015 and 2018. To understand the neutralizing epitopes of H5-HA, we characterized 15 human monoclonal antibodies (mAbs) against the HA of H5 viruses, which were obtained from volunteers who received the H5N1 vaccine that contains a subclade 2.2.1 or 2.1.3.2 virus as an antigen. Twelve mAbs were specific for the HA of subclade 2.2.1, two mAbs were specific for the HA of subclade 2.1.3.2, and one mAb was specific for the HA of both. Of the 15 mAbs analyzed, nine, which were specific for the HA of subclade 2.2.1, and shared the VH and VL genes, possessed hemagglutination inhibition and neutralizing activities, whereas the others did not. A single amino acid substitution or insertion at positions 144-147 in antigenic site A conferred resistance against these nine mAbs to the subclade 2.2.1 viruses. The amino acids at positions 144-147 are highly conserved among subclade 2.2.1, but differ from those of other subclades. These results show that the neutralizing epitope including amino acids at positions 144-147 is targeted by human antibodies, and plays a role in the antigenic difference between subclade 2.2.1 and other subclades.

12.
Nat Microbiol ; 4(6): 1024-1034, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30886361

RESUMO

Influenza viruses possess two surface glycoproteins, haemagglutinin and neuraminidase (NA). Although haemagglutinin plays a major role as a protective antigen, immunity to NA also contributes to protection. The NA protein consists of a stalk and a head portion, the latter of which possesses enzymatic NA (or sialidase) activity. Like haemagglutinin, NA is under immune pressure, which leads to amino acid alterations and antigenic drift. Amino acid changes accumulate around the enzymatic active site, which is located at the top of the NA head. However, amino acid alterations also accumulate at the lateral surface of the NA head. The reason for this accumulation remains unknown. Here, we isolated seven anti-NA monoclonal antibodies (mAbs) from individuals infected with A(H1N1)pdm09 virus. We found that amino acid mutations on the lateral surface of the NA head abolished the binding of all of these mAbs. All seven mAbs activated Fcγ receptor (FcγR)-mediated signalling pathways in effector cells and five mAbs possessed NA inhibition activity, but the other two did not; however, all seven protected mice from lethal challenge infection through their NA inhibition activity and/or FcγR-mediated antiviral activity. Serological analysis of individuals infected with A(H1N1)pdm09 virus revealed that some possessed or acquired the anti-NA-lateral-surface antibodies following infection. We also found antigenic drift on the lateral surface of the NA head of isolates from 2009 and 2015. Our results demonstrate that anti-lateral-surface mAbs without NA inhibition activity can provide protection by activating FcγR-mediated antiviral activity and can drive antigenic drift at the lateral surface of the NA head. These findings have implications for NA antigenic characterization in that they demonstrate that traditional NA inhibition assays are inadequate to fully characterize NA antigenicity.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Vírus da Influenza A/enzimologia , Vírus da Influenza A/imunologia , Neuraminidase/imunologia , Proteínas Virais/imunologia , Animais , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/isolamento & purificação , Antígenos Virais/genética , Antivirais/farmacologia , Modelos Animais de Doenças , Entropia , Epitopos/imunologia , Feminino , Células HEK293 , Humanos , Evasão da Resposta Imune , Imunidade , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A/genética , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Neuraminidase/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Receptores de IgG , Análise de Sequência de Proteína , Proteínas Virais/genética
13.
J Virol ; 93(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30728263

RESUMO

The human B cell response to natural filovirus infections early after recovery is poorly understood. Previous serologic studies suggest that some Ebola virus survivors exhibit delayed antibody responses with low magnitude and quality. Here, we sought to study the population of individual memory B cells induced early in convalescence. We isolated monoclonal antibodies (MAbs) from memory B cells from four survivors treated for Ebola virus disease (EVD) 1 or 3 months after discharge from the hospital. At the early time points postrecovery, the frequency of Ebola-specific B cells was low and dominated by clones that were cross-reactive with both Ebola glycoprotein (GP) and with the secreted GP (sGP) form. Of 25 MAbs isolated from four donors, only one exhibited neutralization activity. This neutralizing MAb, designated MAb EBOV237, recognizes an epitope in the glycan cap of the surface glycoprotein. In vivo murine lethal challenge studies showed that EBOV237 conferred protection when given prophylactically at a level similar to that of the ZMapp component MAb 13C6. The results suggest that the human B cell response to EVD 1 to 3 months postdischarge is characterized by a paucity of broad or potent neutralizing clones. However, the neutralizing epitope in the glycan cap recognized by EBOV237 may play a role in the early human antibody response to EVD and should be considered in rational design strategies for new Ebola virus vaccine candidates.IMPORTANCE The pathogenesis of Ebola virus disease (EVD) in humans is complex, and the mechanisms contributing to immunity are poorly understood. In particular, it appears that the quality and magnitude of the human B cell response early after recovery from EVD may be reduced compared to most viral infections. Here, we isolated human monoclonal antibodies from B cells of four survivors of EVD at 1 or 3 months after hospital discharge. Ebola-specific memory B cells early in convalescence were low in frequency, and the antibodies they encoded demonstrated poor neutralizing potencies. One neutralizing antibody that protected mice from lethal infection, EBOV237, was identified in the panel of 25 human antibodies isolated. Recognition of the glycan cap epitope recognized by EBOV237 suggests that this antigenic site should be considered in vaccine design and treatment strategies for EVD.

14.
J Infect Dis ; 219(Supplement_1): S14-S20, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30715371

RESUMO

Worldwide outbreaks of influenza (pandemics) are caused by influenza A viruses to which persons lack protective immune responses. Currently, we are unable to predict which influenza virus strains may cause a pandemic. In this article, we summarize some of the information that will be needed to better assess the pandemic potential of influenza viruses, and we discuss our current gaps in knowledge.

15.
Viruses ; 11(2)2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30754701

RESUMO

Many cases of human infection with the H7N9 virus have been detected in China since 2013. H7N9 viruses are maintained in chickens and are transmitted to humans at live bird markets. During circulation in birds, H7N9 viruses have accumulated amino acid substitutions in their hemagglutinin (HA), which resulted in an antigenically change in the recent H7N9 viruses. Here, we characterized 46 mouse monoclonal antibodies against the HA of the prototype strain. 16 H7-HA-specific monoclonal antibodies (mAbs) possessed hemagglutination inhibition (HI) and neutralization activities by recognizing the major antigenic site A; four other H7-HA-specific clones also showed HI and neutralizing activities via recognition of the major antigenic sites A and D; seven mAbs that reacted with several HA subtypes and possibly recognized the HA stem partially protected mice from lethal infection with prototype H7N9 virus; and the remaining 19 mAbs had neither HI nor neutralization activity. All human H7N9 viruses tested showed a similar neutralization sensitivity to the first group of 16 mAbs, whereas human H7N9 viruses isolated in 2016‒2017 were not neutralized by a second group of 4 mAbs. These results suggest that amino acid substitutions at the epitope of the second mAb group appear to be involved in the antigenic drift of the H7N9 viruses. Further analysis is required to fully understand the antigenic change in H7N9 viruses.


Assuntos
Anticorpos Monoclonais/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Infecções por Orthomyxoviridae/imunologia , Substituição de Aminoácidos , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Galinhas/virologia , China , Epitopos/imunologia , Feminino , Testes de Inibição da Hemaglutinação , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle
16.
Sci Rep ; 9(1): 1067, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705374

RESUMO

There is large demand for a quantitative method for rapid and ultra-sensitive detection of the influenza virus. Here, we established a digital influenza virus counting (DIViC) method that can detect a single virion without antibody. In the assay, a virion is stochastically entrapped inside a femtoliter reactor array device for the fluorogenic assay of neuraminidase, and incubated for minutes. By analyzing 600,000 reactors, the practical limit of detection reached the order of 103 (PFU)/mL, only 10-times less sensitive than RT-PCR and more than 1000-times sensitive than commercial rapid test kits (RIDTs). Interestingly, neuraminidase activity differed among virions. The coefficient of variance was 30-40%, evidently broader than that of alkaline phosphatase measured as a model enzyme for comparison, suggesting the heterogeneity in size and integrity among influenza virus particles. Sensitivity to oseltamivir also differed between virions. We also tested DIViC using clinical gargle samples that imposes less burden for sampling while with less virus titre. The comparison with RIDTs showed that DIViC was largely superior to RIDTs in the sensitivity with the clinical samples although a few false-positive signals were observed in some clinical samples that remains as a technical challenge.

17.
Euro Surveill ; 24(6)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30755292

RESUMO

BACKGROUND: Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA). Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible. AIM: We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons. METHODS: We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA. We also examined the antigenicity of isolates using ferret antisera obtained from experimentally infected ferrets. RESULTS: Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season. The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades. Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map. CONCLUSION: Multiple clades, some of which differed antigenically from others, co-circulated in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.

19.
Nat Med ; 25(2): 212-220, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30692696

RESUMO

Although antiviral drugs and vaccines have reduced the economic and healthcare burdens of influenza, influenza epidemics continue to take a toll. Over the past decade, research on influenza viruses has revealed a potential path to improvement. The clues have come from accumulated discoveries from basic and clinical studies. Now, virus surveillance allows researchers to monitor influenza virus epidemic trends and to accumulate virus sequences in public databases, which leads to better selection of candidate viruses for vaccines and early detection of drug-resistant viruses. Here we provide an overview of current vaccine options and describe efforts directed toward the development of next-generation vaccines. Finally, we propose a plan for the development of an optimal influenza vaccine.


Assuntos
Vacinas contra Influenza/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Orthomyxoviridae/fisiologia , Pandemias
20.
DNA Cell Biol ; 38(2): 115-120, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30615471

RESUMO

Ebola virus (EBOV) is an enveloped filamentous virus that causes severe hemorrhagic fever in humans and nonhuman primates with up to 90% fatality. Accumulating evidence indicates that various viruses, including EBOV, exploit the host apoptotic clearance machinery to enhance their entry into host cells by externalizing phosphatidylserine (PS) in the viral envelope. PS is typically distributed in the inner layer of the plasma membrane (PM) in normal cells. Progeny EBOV virions bud from the PM of infected cells, suggesting that PS is likely flipped to the outer leaflet of the envelope of Ebola virions. Currently, the intracellular dynamics of PS during EBOV infection are poorly understood. This review summarizes recent progress in determining the molecular mechanism of externalization of PS in the envelope of EBOV particles. We also discuss future directions and how viral apoptotic mimicry could be targeted for therapeutics.


Assuntos
Ebolavirus/metabolismo , Fosfatidilserinas/metabolismo , Proteínas do Envelope Viral/metabolismo , Animais , Membrana Celular/virologia , Doença pelo Vírus Ebola/virologia , Humanos , Vírion/metabolismo
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