scholarly journals Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection

2019 ◽  
Vol 317 (5) ◽  
pp. L591-L601 ◽  
Author(s):  
Rachel Warren ◽  
William Domm ◽  
Min Yee ◽  
Andrew Campbell ◽  
Jane Malone ◽  
...  

Ataxia-telangiectasia (A-T), caused by mutations in the A-T mutated ( ATM) gene, is a neurodegenerative disorder affecting ∼1 in 40,000–100,000 children. Recurrent respiratory infections are a common and challenging comorbidity, often leading to the development of bronchiectasis in individuals with A-T. The role of ATM in development of immune memory in response to recurrent respiratory viral infections is not well understood. Here, we infect wild-type (WT) and Atm-null mice with influenza A virus (IAV; HKx31, H3N2) and interrogate the immune memory with secondary infections designed to challenge the B cell memory response with homologous infection (HKx31) and the T cell memory response with heterologous infection (PR8, H1N1). Although Atm-null mice survived primary and secondary infections, they lost more weight than WT mice during secondary infections. This enhanced morbidity to secondary infections was not attributed to failure to effectively clear virus during the primary IAV infection. Instead, Atm-null mice developed persistent peribronchial inflammation, characterized in part by clusters of B220+ B cells. Additionally, levels of select serum antibodies to hemagglutinin-specific IAV were significantly lower in Atm-null than WT mice. These findings reveal that Atm is required to mount a proper memory response to a primary IAV infection, implying that vaccination of children with A-T by itself may not be sufficiently protective against respiratory viral infections.

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Shabnam Ansari ◽  
Ijhar Ahmad ◽  
Mahboob Ali ◽  
Mohd. Maaz

: “Tiryaq Arba” is a polyherbal Unani formulation in a majoon dosage form that contains four herbal ingredients, namely habbul ghar (Laurus nobilis), juntiyana romi (Gentiana lutea), murr maki (Commiphora myrrha), and zarawand taweel (Aristolochia longa). The medicine has been used as an antidote against different poisons and as a prophylactic medicine before and/or during epidemics. The constituents have been proposed to act as anti-infective, anti-microbial, and antidote against various infectious agents during epidemics (waba). Scientific experimentation of the above-mentioned constituents has also reinforced their beneficial antiviral, immunomodulatory, and antioxidant properties against epidemics of acute respiratory viral infections such as; severe acute respiratory syndrome coronavirus (SARS-CoV), adenovirus, influenza and influenza A virus, respiratory syncytial virus infections, parainfluenza virus, human rhinovirus B, coxsackievirus, parainfluenza virus type 3, Newcastle disease virus, and influenza A virus, which are a greater cause for morbidity and mortality faced by the world, earlier and at present.


2020 ◽  
Vol 92 (3) ◽  
pp. 50-55
Author(s):  
D. A. Lioznov ◽  
E. J. Karnaukhova ◽  
T. G. Zubkova ◽  
E. V. Shakhlanskaya

Aim. To assess the effectiveness of the use of the antiviral drug enisamium iodide in the complex treatment of acute respiratory viral infections (ARVI) caused by various pathogens in routine clinical practice. Materials and methods. А prospective randomized study included 134 patients who were treated in the epidemic season of influenza and ARVI in 20182019. All patients were examined for the presence of influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, rhinoviruses, adenoviruses in nasopharyngeal swabs by PCR. Patients of the main group received enisamium iodide along with symptomatic therapy, the control group received only symptomatic therapy. The primary parameter of the effectiveness of therapy was evaluated on the scale of the general severity of the manifestations of ARVI (Total Symptom Score TSS) from the 2nd to the 4th day and by the secondary criteria of effectiveness: assessment of the duration of ARVI, the severity of fever, the proportion of patients with normal body temperature, the duration of the main clinical symptoms of acute respiratory viral infections, the proportion of patients in whom complications requiring antibiotics were noted, the dynamics of interferon status on the 6th day. To conduct a statistical analysis, depending on the efficiency parameter, the ANCOVA method with a fixed group factor and an initial score on the TSS severity scale was used as covariates, a criterion for comparing quantitative indicators in two independent groups. Results. According to the results of the analysis of the primary efficacy parameter, the median (interquartile range) of the average score on the scale of the general severity of ARVI manifestations in the main group was 4.33 (3.675.83), in the comparison group 6.00 (4.677.25; p0.001). The duration of systemic and local manifestations of acute respiratory viral infections was statistically significantly less in the main group (p=0.002 and p=0.019, respectively). Prescription of additional therapy was required in 2 (2.9%) patients of the main group (patients taking enisamium iodide), compared with 8 (11.9%) patients in the control group. Serum levels of interferon  and interferon  on the last day of treatment were statistically significantly higher in patients of the main group compared with the control group (p0.001). Treatment (excellent) was evaluated by 42 (62.7%) patients, while in the control group only 17 (25.8%) patients gave similar ratings. Both patients (p0.001) and doctors (p0.002) rated therapy tolerance better in the study group. Conclusion. The results confirmed the safety and effectiveness of enisamium iodide as a treatment for ARVI and influenza. The antiviral, interferonogenic and anti-inflammatory properties of the drug are involved in the formation of an antiviral response and reduce the risk of complications, which makes it possible to reduce the number of symptomatic agents used.


2005 ◽  
Vol 289 (1) ◽  
pp. L111-L124 ◽  
Author(s):  
Sabine Teske ◽  
Andrea A. Bohn ◽  
Jean F. Regal ◽  
Joshua J. Neumiller ◽  
B. Paige Lawrence

Unlike their role in bacterial infection, less is known about the role of neutrophils during pulmonary viral infection. Exposure to pollutant 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD, dioxin) results in excess neutrophils in the lungs of mice infected with influenza A virus. TCDD is the most potent agonist for the aryl hydrocarbon receptor (AhR), and exposure to AhR ligands has been correlated with exacerbated inflammatory lung diseases. However, knowledge of the effects of AhR agonists on neutrophils is limited. Likewise, the factors regulating neutrophil responses during respiratory viral infections are not well characterized. To address these knowledge gaps, we determined the in vivo levels of KC, MIP-1α, MIP-2, LIX, IL-6, and C5a in infected mouse lungs. Our data show that these neutrophil chemoattractants are generally produced transiently in the lung within 12–24 h of infection. We also report that expression of CD11a, CD11b, CD49d, CD31, and CD38 is increased on pulmonary neutrophils in response to influenza virus. Using AhR-deficient mice, we demonstrate that excess neutrophilia in the lung is mediated by activation of the AhR and that this enhanced neutrophilia correlates directly with decreased survival in TCDD-exposed mice. Although AhR activation results in more neutrophils in the lungs, we show that this is not mediated by deregulation in levels of common neutrophil chemoattractants, expression of adhesion molecules on pulmonary neutrophils, or delayed death of neutrophils. Likewise, exposure to TCDD did not enhance pulmonary neutrophil function. This study provides an important first step in elucidating the mechanisms by which AhR agonists exacerbate pulmonary inflammatory responses.


2015 ◽  
Vol 7 (02) ◽  
pp. 134-136 ◽  
Author(s):  
Ankit Gupta ◽  
Malini R Capoor ◽  
Sonal Gupta ◽  
Harish Chand Sachdeva

ABSTRACTRespiratory viral infections, especially influenza have a potential to form a fatal association with cryptococcosis in the setting of compromised immunity. Considering the lethality of these two infections, we report an unusual case of dual infection of pandemic influenza A H1N1 and disseminated cryptococcosis in an HIV seropositive individual.


2019 ◽  
Author(s):  
Augustina Sylverken ◽  
Philip El-Duah ◽  
Michael Owusu ◽  
Richmond Yeboah ◽  
Alexander Kwarteng ◽  
...  

Abstract Respiratory viral infections are important causes of morbidity and mortality worldwide. Information on circulating respiratory viruses among prisoners is lacking, although this is of public health importance and knowledge would assist in putting in place preventive measures to forestall disease outbreaks. The aim of this study therefore was to get the footprint of such diseases that have epidemic potential to be described and quantified for control. Prisoners on remand numbering 203 in a prison in Kumasi, the Ashanti Regional capital, were interviewed using prevalidated questionnaire, nasopharyngeal samples taken and screened by real-time PCR for common respiratory viruses in February, 2018. Of the total number of 203 participants enrolled, majority were males (n = 198, 97.54%). The modal age unsurprisingly was in the active working class of 18 to 35 years (n = 155, 76.36%) with 48 (23.65%) of participants older than 35 years. Inmates reported nasal congestion (n = 83, 40.89%), cough with or without pharyngitis (n =108, 53.20%) and fever (n = 74, 39.48%). Viruses detected in throat samples were Influenza A (n = 1, 0.49%) and Rhinovirus (n = 8, 3.94%). There was no statistically significant association between respiratory virus positivity and age (p = 0.118), gender (p > 0.900), duration of incarceration (p = 0.239) and reported symptoms (p = 0.724). The prison population may have a lower prevalence of respiratory viruses circulating in them. This may be dominated by those with high antigenic diversity.


2003 ◽  
Vol 77 (14) ◽  
pp. 7756-7763 ◽  
Author(s):  
Haiyan Liu ◽  
Samita Andreansky ◽  
Gabriela Diaz ◽  
Stephen J. Turner ◽  
Dominik Wodarz ◽  
...  

ABSTRACT The consequences for the long-term maintenance of virus-specific CD8+-T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [γHV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8+ T cells specific for the prominent influenza virus DbNP366 epitope were reduced by about half in mice that had been challenged 100 days previously with γHV68, though the prior presence of a large CD8+ DbNP366 + population caused no selective defect in the γHV68-specific CD8+ Kbp79+ response. Conversely, mice that had been primed and boosted to generate substantial γHV68-specific CD8+ Dbp56+ populations did not show any decrease in prevalence for this set of CD8+ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8+-T-cell pool was significantly diminished in those that had been infected with γHV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory “phenome” is a function of the overall infection experience of the individual.


2017 ◽  
Vol 131 (14) ◽  
pp. 1737-1762 ◽  
Author(s):  
S. Rameeza Allie ◽  
Troy D. Randall

Mucosal surfaces, such as the respiratory epithelium, are directly exposed to the external environment and therefore, are highly susceptible to viral infection. As a result, the respiratory tract has evolved a variety of innate and adaptive immune defenses in order to prevent viral infection or promote the rapid destruction of infected cells and facilitate the clearance of the infecting virus. Successful adaptive immune responses often lead to a functional state of immune memory, in which memory lymphocytes and circulating antibodies entirely prevent or lessen the severity of subsequent infections with the same virus. This is also the goal of vaccination, although it is difficult to vaccinate in a way that mimics respiratory infection. Consequently, some vaccines lead to robust systemic immune responses, but relatively poor mucosal immune responses that protect the respiratory tract. In addition, adaptive immunity is not without its drawbacks, as overly robust inflammatory responses may lead to lung damage and impair gas exchange or exacerbate other conditions, such as asthma or chronic obstructive pulmonary disease (COPD). Thus, immune responses to respiratory viral infections must be strong enough to eliminate infection, but also have mechanisms to limit damage and promote tissue repair in order to maintain pulmonary homeostasis. Here, we will discuss the components of the adaptive immune system that defend the host against respiratory viral infections.


2000 ◽  
Vol 74 (24) ◽  
pp. 11690-11696 ◽  
Author(s):  
Jan P. Christensen ◽  
Peter C. Doherty ◽  
Kristen C. Branum ◽  
Janice M. Riberdy

ABSTRACT The recall of CD8+ T-cell memory established by infecting H-2b mice with an H1N1 influenza A virus provided a measure of protection against an extremely virulent H7N7 virus. The numbers of CD8+ effector and memory T cells specific for the shared, immunodominant DbNP366epitope were greatly increased subsequent to the H7N7 challenge, and though lung titers remained as high as those in naive controls for 5 days or more, the virus was cleared more rapidly. Expanding the CD8+ memory T-cell pool (<0.5 to >10%) by sequential priming with two different influenza A viruses (H3N2→H1N1) gave much better protection. Though the H7N7 virus initially grew to equivalent titers in the lungs of naive and double-primed mice, the replicative phase was substantially controlled within 3 days. This tertiary H7N7 challenge caused little increase in the magnitude of the CD8+ DbNP366 + T-cell pool, and only a portion of the memory population in the lymphoid tissue could be shown to proliferate. The great majority of the CD8+ DbNP366 + set that localized to the infected respiratory tract had, however, cycled at least once, though recent cell division was shown not to be a prerequisite for T-cell extravasation. The selective induction of CD8+ T-cell memory can thus greatly limit the damage caused by a virulent influenza A virus, with the extent of protection being directly related to the number of available responders. Furthermore, a large pool of CD8+ memory T cells may be only partially utilized to deal with a potentially lethal influenza infection.


1999 ◽  
Vol 73 (2) ◽  
pp. 1453-1459 ◽  
Author(s):  
Janice M. Riberdy ◽  
Kirsten J. Flynn ◽  
Juergen Stech ◽  
Robert G. Webster ◽  
John D. Altman ◽  
...  

ABSTRACT The question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian H5N1 virus in Hong Kong. The likely strategy would be to vaccinate with a less virulent, laboratory-adapted H5N1 strain isolated previously from birds. Little attention has been given, however, to dissecting the consequences of sequential exposure to serologically related influenza A viruses using contemporary immunology techniques. Such experiments with the H5N1 viruses are limited by the potential risk to humans. An extremely virulent H3N8 avian influenza A virus has been used to infect both immunoglobulin-expressing (Ig+/+) and Ig−/− mice primed previously with a laboratory-adapted H3N2 virus. The cross-reactive antibody response was very protective, while the recall of CD8+ T-cell memory in the Ig−/− mice provided some small measure of resistance to a low-dose H3N8 challenge. The H3N8 virus also replicated in the respiratory tracts of the H3N2-primed Ig+/+ mice, generating secondary CD8+ and CD4+ T-cell responses that may contribute to recovery. The results indicate that the various components of immune memory operate together to provide optimal protection, and they support the idea that related viruses of nonhuman origin can be used as vaccines.


2017 ◽  
Vol 89 (1) ◽  
pp. 62-71 ◽  
Author(s):  
V A Bulgakova ◽  
A A Poromov ◽  
A I Grekova ◽  
N Yu Pshenichnaya ◽  
E P Selkova ◽  
...  

Aim. To identify risk factors (RFs) for the development of bacterial complications and the prolonged course of influenza and other acute respiratory viral infections (ARVIs) among inpatients treated in Russian healthcare facilities in the post-pandemic period; to determine the clinical presentation of the disease (flu-like syndrome) in risk-group people and to evaluate the efficacy of antiviral therapy with arbidol (umifenovir). Materials and methods. The investigators retrospectively analyzed randomly selected medical records of inpatients with influenza and other ARVI in 88 hospitals from 50 regions of the Russian Federation: those of 3532 and 1755 patients in the 2010-2011 and 2014-2015 seasons, respectively, by applying parametric and nonparametric statistical methods. Results. The built database of patients with influenza-like syndrome contained data from the histories of 2072 men and 2537 women, of whom there were 317 (12.49%) pregnant women; gender evidence was not given in the medical records for 678 patients. 382 (7.2%) were vaccinated against influenza. 1528 (28.9%) people were admitted to hospital with various complications. Information on laboratory tests was available in 1691 (31.98%) patients; of these, 1291 (76.4%) were detected to have influenza and other respiratory viruses. Influenza viruses were found in 1026 (60.7%) examinees; influenza A viruses in 712 (42.1%) people while pandemic strain of swine influenza A/H1N1 and A/H3N2 viruses was detected in 487 (28.8%) and 107 (6.3%) patients, respectively; influenza A subtype was indicated in 118 (7%) persons with laboratory-confirmed influenza virus. Influenza B viruses were found in 314 (18.6%) examinees. Other types of respiratory viruses were detected in 265 (15.7%) patients. The body mass index exceeded 30 kg/m2 in 227 (4.3%) patients. Single-factor analysis of variance revealed factors influencing the course of flu-like syndrome and identified risk groups: children younger than 2 years old and adults over 65, pregnant women, and people with chronic somatic diseases and obesity. The high-risk groups exhibited a more severe course of flu-like syndrome than did the patients outside the risk groups. The incidence of complications was higher, especially in the under 2-year-year-old children and in patients with endocrine, metabolic, or respiratory diseases, with a large proportion of complications being pneumonia. The efficacy of antiviral therapy was higher in the elderly, patients with chronic diseases, and pregnant women than in patients not at risk. In patients treated with umifenovir (provided that it was administered in the first 48 hours after disease onset), the duration of fever and frequency of complications proved to be lower than those in patients who did not receive antiviral therapy. Conclusion. The FRs for influenza and ARVI complications are patient’s age (children under 3 years of age and adults older than 65 years), the presence of chronic somatic diseases, and pregnancy. Patients with endocrine, eating, metabolic (including obesity), circulatory, and respiratory disorders are at high risk for influenza and ARVI complications. Umifenovir therapy substantially reduces the duration of fever and risk of complications, especially in patients with laboratory-confirmed influenza infection


Sign in / Sign up

Export Citation Format

Share Document