scholarly journals Role of Memory B Cells in Hemagglutinin-Specific Antibody Production Following Human Influenza A Virus Infection

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 167 ◽  
Author(s):  
Mark Y. Sangster ◽  
Phuong Q. T. Nguyen ◽  
David J. Topham
Keyword(s):  
B Cells ◽  
Virus Infection ◽  
Antibody Response ◽  
Influenza A Virus ◽  
Antibody Production ◽  
Specific Antibody ◽  
Germinal Center ◽  
Influenza A ◽  
Influenza Virus Infection

When influenza A virus infects an immune individual, preexisting memory B cell (MBC) activation and rapid anamnestic antibody production plays a key role in viral clearance. The most effective neutralizing antibodies target the antigenically variable head of the viral hemagglutinin (HA); antibodies against the conserved HA stalk provide broader but less potent protection. In this review, we provide a comprehensive picture of an adult’s HA-specific antibody response to influenza virus infection. The process is followed from preexisting HA-specific MBC activation and rapid production of anti-HA antibodies, through to germinal center seeding and adaptation of the response to novel features of the HA. A major focus of the review is the role of competition between preexisting MBCs in determining the character of the HA-reactive antibody response. HA novelty modifies this competition and can shift the response from the immunodominant head to the stalk. We suggest that antibodies resulting from preexisting MBC activation are important regulators of anti-HA antibody production and play a role in positive selection of germinal center B cells reactive to novel HA epitopes. Our review also considers the role of MBCs in the effects of early-life imprinting on HA head- and stalk-specific antibody responses to influenza infection. An understanding of the processes described in this review will guide development of vaccination strategies that provide broadly effective protection.

scholarly journals CD83 Expression Regulates Antibody Production in Response to Influenza A Virus Infection

2020 ◽  
Author(s):  
Madhav Akauliya ◽  
Avishekh Gautam ◽  
Sony Maharjan ◽  
Byoung Kwon Park ◽  
Jinsoo Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Cell Population ◽  
Peritoneal Cavity ◽  
Antibody Production ◽  
Influenza A ◽  
Wild Type ◽  
Influenza A Virus Infection

Abstract Background: CD83 is known to regulate lymphocyte maturation, activation, homeostasis, and antibody response to immunization and infection. While CD83 has a major part in B cell function, its role in influenza A virus infection has not yet been investigated. Methods: We investigated the role of CD83 using C57BL/6J wild type mice and CD83 knockout (KO) mice after intraperitoneal administration of the influenza A/WSN/1933 virus. We analyzed cells of the peritoneal cavity, splenocytes, and cells of the bone marrow with FACS to investigate CD83 expression and cell population change in response to the virus infection. ELISA was performed with sera and peritoneal cavity fluids to detect A/WSN/1933 virus-specific IgG and the subclasses of IgG. Results: FACS analysis data showed a transient but distinct induction of CD83 expression in the peritoneal B cells of wild type mice. CD83 KO mice exhibited a delayed recovery of B cells in the bone marrow after influenza virus infection and overall, a smaller T cell population compared to wild type mice. The peritoneal cavity and serum of the wild type mice contained a high titer of IgG within 14 days after infection, whereas the CD83 KO mice had a very low titer of IgG. Conclusions: These results show the importance of CD83 in lymphocytes homeostasis and antibody production during influenza A virus infection.

scholarly journals CD83 expression regulates antibody production in response to influenza A virus infection

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Madhav Akauliya ◽  
Avishekh Gautam ◽  
Sony Maharjan ◽  
Byoung Kwon Park ◽  
Jinsoo Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Cell Population ◽  
Peritoneal Cavity ◽  
Antibody Production ◽  
Influenza A ◽  
Wild Type ◽  
Influenza A Virus Infection

Abstract Background CD83 is known to regulate lymphocyte maturation, activation, homeostasis, and antibody response to immunization and infection. While CD83 has a major part in B cell function, its role in influenza A virus infection has not yet been investigated. Methods We investigated the role of CD83 using C57BL/6J wild type mice and CD83 knockout (KO) mice after intraperitoneal administration of the influenza A/WSN/1933 virus. We analyzed cells of the peritoneal cavity, splenocytes, and cells of the bone marrow with FACS to investigate CD83 expression and cell population change in response to the virus infection. ELISA was performed with sera and peritoneal cavity fluids to detect A/WSN/1933 virus-specific IgG and the subclasses of IgG. Results FACS analysis data showed a transient but distinct induction of CD83 expression in the peritoneal B cells of wild type mice. CD83 KO mice exhibited a delayed recovery of B cells in the bone marrow after influenza virus infection and overall, a smaller T cell population compared to wild type mice. The peritoneal cavity and serum of the wild type mice contained a high titer of IgG within 14 days after infection, whereas the CD83 KO mice had a very low titer of IgG. Conclusions These results show the importance of CD83 in lymphocytes homeostasis and antibody production during influenza A virus infection.

scholarly journals CD83 expression regulates antibody production in response to influenza A virus infection

2020 ◽  
Author(s):  
Madhav Akauliya ◽  
Avishekh Gautam ◽  
Sony Maharjan ◽  
Byoung Kwon Park ◽  
Jinsoo Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Cell Population ◽  
Peritoneal Cavity ◽  
Antibody Production ◽  
Influenza A ◽  
Wild Type ◽  
Influenza A Virus Infection

Abstract Background: CD83 is known to regulate lymphocyte maturation, activation, homeostasis, and antibody response to immunization and infection. While CD83 has a major part in B cell function, its role in influenza A virus infection has not yet been investigated. Methods: We investigated the role of CD83 using C57BL/6J wild type mice and CD83 knockout (KO) mice after intraperitoneal administration of the influenza A/WSN/1933 virus. We analyzed cells of the peritoneal cavity, splenocytes, and cells of the bone marrow with FACS to investigate CD83 expression and cell population change in response to the virus infection. ELISA was performed with sera and peritoneal cavity fluids to detect A/WSN/1933 virus-specific IgG and the subclasses of IgG. Results: FACS analysis data showed a transient but distinct induction of CD83 expression in the peritoneal B cells of wild type mice. CD83 KO mice exhibited a delayed recovery of B cells in the bone marrow after influenza virus infection and overall, a smaller T cell population compared to wild type mice. The peritoneal cavity and serum of the wild type mice contained a high titer of IgG within 14 days after infection, whereas the CD83 KO mice had a very low titer of IgG. Conclusions: These results show the importance of CD83 in lymphocytes homeostasis and antibody production during influenza A virus infection.

scholarly journals The Role of Alpha/Beta and Gamma Interferons in Development of Immunity to Influenza A Virus in Mice

2000 ◽  
Vol 74 (9) ◽  
pp. 3996-4003 ◽  
Author(s):  
Graeme E. Price ◽  
Anna Gaszewska-Mastarlarz ◽  
Demetrius Moskophidis
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Antibody Responses ◽  
Adaptive Immune ◽  
Ifn Γ ◽  
Alpha Beta

ABSTRACT During influenza virus infection innate and adaptive immune defenses are activated to eliminate the virus and thereby bring about recovery from illness. Both arms of the adaptive immune system, antibody neutralization of free virus and termination of intracellular virus replication by antiviral cytotoxic T cells (CTLs), play pivotal roles in virus elimination and protection from disease. Innate cytokine responses, such as alpha/beta interferon (IFN-α/β) or IFN-γ, can have roles in determining the rate of virus replication in the initial stages of infection and in shaping the initial inflammatory and downstream adaptive immune responses. The effect of these cytokines on the replication of pneumotropic influenza A virus in the respiratory tract and in the regulation of adaptive antiviral immunity was examined after intranasal infection of mice with null mutations in receptors for IFN-α/β, IFN-γ, and both IFNs. Virus titers in the lungs of mice unable to respond to IFNs were not significantly different from congenic controls for both primary and secondary infection. Likewise the mice were comparably susceptible to X31 (H3N2) influenza virus infection. No significant disruption to the development of normal antiviral CTL or antibody responses was observed. In contrast, mice bearing the disrupted IFN-α/β receptor exhibited accelerated kinetics and significantly higher levels of neutralizing antibody activity during primary or secondary heterosubtypic influenza virus infection. Thus, these observations reveal no significant contribution for IFN-controlled pathways in shaping acute or memory T-cell responses to pneumotropic influenza virus infection but do indicate some role for IFN-α/β in the regulation of antibody responses. Recognizing the pivotal role of CTLs and antibody in virus clearance, it is reasonable to assume a redundancy in IFN-mediated antiviral effects in pulmonary influenza. However, IFN-α/β seems to be a valid factor in determining tissue tropism and replicative rates of highly virulent influenza virus strains as reported previously by others, and this aspect is discussed here.

scholarly journals TNK2/ACK1 Strengthen Influenza A Virus Infection by Blocking Viral Matrix 2 Protein(M2) into Lysosome to Degradation

2021 ◽  
Author(s):  
Ao Zhou ◽  
Xia Dong ◽  
Bin Tang
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Protein Trafficking ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Wild Type ◽  
Genome Wide ◽  
Mutant Cells

Abstract BackgroundTNK2/ACK1, a non-receptor tyrosine kinase, plays critical roles in signalling transduces and trafficking. Our previous genome-wide CRISPR/CAS9 knockout screen revealed that mutant of TNK2 produced more restrict to influenza virus infection. In this study, we aim to illustrate the role of TNK2 for influenza A virus (IAV) replication in human cells.ResultsCRISPR/Cas9-mediated mutant of TNK2 resulted in a significant reduction in viral proteins expression and viral titres for multiple influenza strains, and furthermore, a decrease of nuclear import of IAV in the infected TNK2 mutant cells was observed in 3h post-infection. Interestingly, TNK2 mutation enhanced the colocalization of LC3 with autophagic receptor p62 and led to the attenuation of influenza virus-caused accumulation of autophagosomes in TNK2 mutant cells. Further, confocal microscopy visualization result showed that influenza viral matrix 2 (M2) was colocalized with Lamp1 in the infected TNK2 mutant cells in early infection, while almost no colocalization between M2 and Lamp1 was observed in IAV-infected wild-type cells. Moreover, TNK2 depletion also affected the trafficking of early endosome and the movement of influenza viral NP and M2.ConclusionsOur results identified TNK2 as a critical host factor for influenza viral M2 protein trafficking, suggesting that TNK2 will be an attractive target for the development of antivirals therapeutics.

Role of the chaperone protein 14-3-3ε in the regulation of influenza A virus-activated beta interferon

2021 ◽  
Author(s):  
Ee-Hong Tam ◽  
Yen-Chin Liu ◽  
Chian-Huey Woung ◽  
Helene Minyi Liu ◽  
Guan-Hong Wu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Ns1 Protein ◽  
Chaperone Protein ◽  
Influenza A Virus Infection

The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in RIG-I translocation to MAVS to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-β promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-β expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49 th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C-terminus-truncated NS1 with T49A mutation dramatically increases IFN-β mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-β expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in RIG-I translocation that induces type I IFN expression, and that NS1 protein prevents RIG-I translocation to mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-β suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection.

Defense against Influenza A Virus Infection: Essential Role of the Chemokine System

Immunobiology ◽  
2001 ◽  
Vol 204 (5) ◽  
pp. 603-613 ◽  
Author(s):  
A KAUFMANN
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Essential Role ◽  
Influenza A Virus Infection

scholarly journals Routine blood parameters are helpful for early identification of influenza infection in children

2020 ◽  
Author(s):  
Ronghe Zhu ◽  
Cuie Chen ◽  
Qiu Wang ◽  
Xixi Zhang ◽  
Chaosheng Lu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Early Identification ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Cutoff Value ◽  
Routine Blood ◽  
Influenza A Virus Infection

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection.Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.

scholarly journals Broad Hemagglutinin-Specific Memory B Cell Expansion by Seasonal Influenza Virus Infection Reflects Early-Life Imprinting and Adaptation to the Infecting Virus

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Brenda L. Tesini ◽  
Preshetha Kanagaiah ◽  
Jiong Wang ◽  
Megan Hahn ◽  
Jessica L. Halliley ◽  
...  
Keyword(s):  
Influenza Virus ◽  
B Cells ◽  
Virus Infection ◽  
B Cell ◽  
Specific Antibody ◽  
Early Life ◽  
Influenza Virus Infection ◽  
Memory B Cells ◽  
Specific Memory ◽  
Original Antigenic Sin

ABSTRACTMemory B cells (MBCs) are key determinants of the B cell response to influenza virus infection and vaccination, but the effect of different forms of influenza antigen exposure on MBC populations has received little attention. We analyzed peripheral blood mononuclear cells and plasma collected following human H3N2 influenza infection to investigate the relationship between hemagglutinin-specific antibody production and changes in the size and character of hemagglutinin-reactive MBC populations. Infection produced increased concentrations of plasma IgG reactive to the H3 head of the infecting virus, to the conserved stalk, and to a broad chronological range of H3s consistent with original antigenic sin responses. H3-reactive IgG MBC expansion after infection included reactivity to head and stalk domains. Notably, expansion of H3 head-reactive MBC populations was particularly broad and reflected original antigenic sin patterns of IgG production. Findings also suggest that early-life H3N2 infection “imprints” for strong H3 stalk-specific MBC expansion. Despite the breadth of MBC expansion, the MBC response included an increase in affinity for the H3 head of the infecting virus. Overall, our findings indicate that H3-reactive MBC expansion following H3N2 infection is consistent with maintenance of response patterns established early in life, but nevertheless includes MBC adaptation to the infecting virus.IMPORTANCERapid and vigorous virus-specific antibody responses to influenza virus infection and vaccination result from activation of preexisting virus-specific memory B cells (MBCs). Understanding the effects of different forms of influenza virus exposure on MBC populations is therefore an important guide to the development of effective immunization strategies. We demonstrate that exposure to the influenza hemagglutinin via natural infection enhances broad protection through expansion of hemagglutinin-reactive MBC populations that recognize head and stalk regions of the molecule. Notably, we show that hemagglutinin-reactive MBC expansion reflects imprinting by early-life infection and that this might apply to stalk-reactive, as well as to head-reactive, MBCs. Our findings provide experimental support for the role of MBCs in maintaining imprinting effects and suggest a mechanism by which imprinting might confer heterosubtypic protection against avian influenza viruses. It will be important to compare our findings to the situation after influenza vaccination.

Matrix Metalloproteinase-13 in Atherosclerotic Plaque Is Increased by Influenza A Virus Infection

2019 ◽  
Vol 221 (2) ◽  
pp. 256-266 ◽  
Author(s):  
Han Sol Lee ◽  
Ji Yun Noh ◽  
Ok Sarah Shin ◽  
Joon Young Song ◽  
Hee Jin Cheong ◽  
...  
Keyword(s):  
Virus Infection ◽  
Western Blot ◽  
Influenza A Virus ◽  
Atherosclerotic Plaque ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Mapk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Influenza A Virus Infection ◽  
Deficient Mice

Abstract Background Influenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear. Methods We examined the expression levels of matrix metalloproteinases (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot. Results We confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions In this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.

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