scholarly journals Gamma Interferon Is Not Required for Mucosal Cytotoxic T-Lymphocyte Responses or Heterosubtypic Immunity to Influenza A Virus Infection in Mice

2000 ◽  
Vol 74 (12) ◽  
pp. 5495-5501 ◽  
Author(s):  
Huan H. Nguyen ◽  
Frederik W. van Ginkel ◽  
Huong L. Vu ◽  
Miroslav J. Novak ◽  
Jerry R. McGhee ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Gamma Interferon ◽  
Necrosis Factor Alpha ◽  
Virus Challenge ◽  
Heterosubtypic Immunity ◽  
Ifn Γ ◽  
Influenza A Virus Infection

ABSTRACT Heterosubtypic immunity (HSI) is defined as cross-protection against influenza virus of a different serotype than the virus initially encountered and is thought to be mediated by influenza virus-specific cytotoxic T lymphocytes (CTL). Since gamma interferon (IFN-γ) stimulates cytotoxic cells, including antigen-specific CTL which may control virus replication by secretion of antiviral cytokines such as tumor necrosis factor alpha and IFN-γ, we have investigated the mechanism of HSI by analyzing the role of IFN-γ for HSI in IFN-γ gene-deleted (IFN-γ−/−) mice. It has been reported that IFN-γ is not required for recovery from primary infection with influenza virus but is important for HSI. Here, we conclusively show that IFN-γ is not required for induction of secondary influenza virus-specific CTL responses in mediastinal lymph nodes and HSI to lethal influenza A virus infection. Although T helper 2 (Th2)-type cytokines were upregulated in the lungs of IFN-γ−/− mice after virus challenge, either Th1- or Th2-biased responses could provide heterosubtypic protection. Furthermore, titers of serum-neutralizing and cross-reactive antibodies to conserved nucleoprotein in IFN-γ−/− mice did not differ significantly from those in immunocompetent mice. These results indicate that lack of IFN-γ does not impair cross-reactive virus-specific immune responses and HSI to lethal infection with influenza virus. Our findings provide new insight for the mechanisms of HSI and should be valuable in the development of protective mucosal vaccines against variant virus strains, such as influenza and human immunodeficiency virus.

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 Microbiome disturbance and resilience dynamics of the upper respiratory tract in response to influenza A virus infection in humans and ferrets

2018 ◽  
Author(s):  
Drishti Kaul ◽  
Raveen Rathnasinghe ◽  
Marcela Ferres ◽  
Gene S. Tan ◽  
Aldo Barrera ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cellular Damage ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Influenza A Virus Infection ◽  
Over Time

AbstractInfection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation because of host responses and cellular damage. The native upper respiratory tract (URT) microbiome likely plays a role, yet the effects of influenza infection on the URT microbiome are largely unknown. We performed a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes had stable “heathy ecostate” communities both within and between individuals. In contrast, infected patients and ferrets exhibited large changes in bacterial community composition over time and between individuals. The “unhealthy” ecostates of infected individuals progressed towards the “healthy ecostate” over time, coinciding with viral clearance and recovery. Blooms of Pseudomonas were a statistically associated constant in the disturbed microbiomes of infected individuals. The dynamic and resilient nature of the microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.One Sentence SummaryDynamics of the upper respiratory tract microbiome during influenza A virus infection

scholarly journals Routine blood parameters can detect early influenza virus infection in children

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

Abstract Purpose We aimed to explore the value of 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, for predicting influenza virus infection in children. Methods We conducted a single-center, retrospective, observational study on fever with influenza-like symptom in pediatric outpatients in different age groups and evaluated the predictive value of various routine blood parameters within 48 hours of the onset of fever after influenza virus infection. Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in the infected children. The LYM count, LMR and LYM*PLT in the infected group were lower in the 1- to 6-year-old group, and the LMR and LYM*PLT in the infected group were lower in the > 6-year-old group. In the 1- to 6-year-old group, 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 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 group, 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 predicting influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, especially influenza A virus infection.

scholarly journals Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Guihong Yang ◽  
Huipeng Huang ◽  
Mengyao Tang ◽  
Zifeng Cai ◽  
Cuiqin Huang ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
A549 Cells ◽  
Virus Challenge ◽  
Neuromedin B ◽  
Influenza A Virus Infection

Abstract The peptide neuromedin B (NMB) and its receptor (NMBR) represent a system (NMB/NMBR) of neuromodulation. Here, it was demonstrated that the expression of NMBR in cells or murine lung tissues was clearly upregulated in response to H1N1/PR8 influenza A virus infection. Furthermore, the in vitro and in vivo activities of NMB/NMBR during PR8 infection were investigated. It was observed that A549 cells lacking endogenous NMBR were more susceptible to virus infection than control cells, as evidenced by the increased virus production in the cells. Interestingly, a significant decrease in IFN-α and increased IL-6 expression were observed in these cells. The role of this system in innate immunity against PR8 infection was probed by treating mice with NMB. The NMB-treated mice were less susceptible to virus challenge, as evidenced by increased survival, increased body weight, and decreased viral NP expression compared with the control animals. Additionally, the results showed that exogenous NMB not only enhanced IFN-α expression but also appeared to inhibit the expression of NP and IL-6 in PR8-infected cells and animals. As expected, opposing effects were observed in the NMBR antagonist-treated cells and mice, which further confirmed the effects of NMB. Together, these data suggest that NMB/NMBR may be an important component of the host defence against influenza A virus infection. Thus, these proteins may serve as promising candidates for the development of novel antiviral drugs.

scholarly journals Histone Deacetylase 6 Knockout Mice Exhibit Higher Susceptibility to Influenza A Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 728 ◽  
Author(s):  
Mark Zanin ◽  
Jennifer DeBeauchamp ◽  
Gowthami Vangala ◽  
Richard J. Webby ◽  
Matloob Husain
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Histone Deacetylase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antiviral Response ◽  
Histone Deacetylase 6 ◽  
Influenza A Virus Infection ◽  
Innate Antiviral Response ◽  
Mouse Lungs

The host innate defence against influenza virus infection is an intricate system with a plethora of antiviral factors involved. We have identified host histone deacetylase 6 (HDAC6) as an anti-influenza virus factor in cultured cells. Consistent with this, we report herein that HDAC6 knockout (KO) mice are more susceptible to influenza virus A/PR/8/1934 (H1N1) infection than their wild type (WT) counterparts. The KO mice lost weight faster than the WT mice and, unlike WT mice, could not recover their original body weight. Consequently, more KO mice succumbed to infection, which corresponded with higher lung viral loads. Conversely, the expression of the critical innate antiviral response genes interferon alpha/beta, CD80, CXCL10 and IL15 was significantly downregulated in KO mouse lungs compared to WT mouse lungs. These data are consistent with the known function of HDAC6 of de-acetylating the retinoic acid inducible gene-I (RIG-I) and activating the host innate antiviral response cascade. Loss of HDAC6 thus leads to a blunted innate response and increased susceptibility of mice to influenza A virus infection.

Mechanism of heterosubtypic immunity to influenza A virus infection

2001 ◽  
Vol 1219 ◽  
pp. 333-340 ◽  
Author(s):  
Huan H Nguyen ◽  
Frederik W van Ginkel ◽  
Huong L Vu ◽  
Jerry R McGhee ◽  
Jiri Mestecky
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Heterosubtypic Immunity ◽  
Influenza A Virus Infection

scholarly journals Characterization of a new H-2Dk-restricted epitope prominent in primary influenza A virus infection

2001 ◽  
Vol 82 (7) ◽  
pp. 1749-1755 ◽  
Author(s):  
Sophie Tourdot ◽  
Shan Herath ◽  
Keith G. Gould
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Dominance Hierarchy ◽  
Influenza Virus Infection ◽  
Amino Acid Residues ◽  
Influenza A Virus Infection ◽  
Restricted Epitope

Influenza A virus infection of mice has been used extensively as a model to investigate the mechanisms of antigen presentation to cytotoxic T lymphocytes (CTL) and the phenomenon of immunodominance in antiviral CTL responses. The different virus-encoded epitopes that are recognized in H-2b and H-2d mice have been characterized and their relative immunodominance has been well-studied. In H-2k mice, four different Kk-restricted influenza virus epitopes have been described, but the dominance hierarchy of these epitopes is unknown and there is also an uncharacterized Dk-restricted response against the virus. In this study, a Dk-restricted epitope derived from the influenza virus A/PR/8/34 polymerase protein PB1, corresponding to amino acid residues 349–357 (ARLGKGYMF), was identified. This peptide is the major epitope within the PB1 polymerase and is at least as dominant as any of the four Kk-restricted epitopes that are recognized in CBA mice following primary influenza virus infection. The PB1 epitope is only the fourth Dk-presented peptide to be reported and the sequence of this epitope confirms a Dk-restricted peptide motif, consisting of arginine at position two, arginine or lysine at position five and a hydrophobic residue at the carboxy terminus.

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.

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