scholarly journals How sticky should a virus be? The impact of virus binding and release on transmission fitness using influenza as an example

2014 ◽  
Vol 11 (92) ◽  
pp. 20131083 ◽  
Author(s):  
Andreas Handel ◽  
Victoria Akin ◽  
Sergei S. Pilyugin ◽  
Veronika Zarnitsyna ◽  
Rustom Antia
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Virus Binding ◽  
Adaptive Immune ◽  
Cell Mediated Immune Response ◽  
Infected Cells ◽  
The Right ◽  
The Impact ◽  
Virus Fitness ◽  
Better Than

Budding viruses face a trade-off: virions need to efficiently attach to and enter uninfected cells while newly generated virions need to efficiently detach from infected cells. The right balance between attachment and detachment—the right amount of stickiness—is needed for maximum fitness. Here, we design and analyse a mathematical model to study in detail the impact of attachment and detachment rates on virus fitness. We apply our model to influenza, where stickiness is determined by a balance of the haemagglutinin (HA) and neuraminidase (NA) proteins. We investigate how drugs, the adaptive immune response and vaccines impact influenza stickiness and fitness. Our model suggests that the location in the ‘stickiness landscape’ of the virus determines how well interventions such as drugs or vaccines are expected to work. We discuss why hypothetical NA enhancer drugs might occasionally perform better than the currently available NA inhibitors in reducing virus fitness. We show that an increased antibody or T-cell-mediated immune response leads to maximum fitness at higher stickiness. We further show that antibody-based vaccines targeting mainly HA or NA, which leads to a shift in stickiness, might reduce virus fitness above what can be achieved by the direct immunological action of the vaccine. Overall, our findings provide potentially useful conceptual insights for future vaccine and drug development and can be applied to other budding viruses beyond influenza.

scholarly journals Rapid Weight Loss, Central Obesity Improvement and Blood Glucose Reduction Are Associated with a Stronger Adaptive Immune Response Following COVID-19 mRNA Vaccine

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 79
Author(s):  
Mikiko Watanabe ◽  
Angela Balena ◽  
Davide Masi ◽  
Rossella Tozzi ◽  
Renata Risi ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Blood Glucose ◽  
Adaptive Immune Response ◽  
Humoral Response ◽  
Rapid Weight Loss ◽  
Low Carbohydrate Diet ◽  
Adaptive Immune ◽  
Glucose Reduction ◽  
The Impact

Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet’s safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R −0.558, p = 0.013 for IFNγ-1; R −0.581, p = 0.009 for IFNγ-2; R −0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

scholarly journals Immune Response to COVID-19

2021 ◽  
Author(s):  
Ricardo Wesley Alberca
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Multiple Organ ◽  
Disease Course ◽  
Angiotensin Converting Enzyme 2 ◽  
Damage And Failure ◽  
Adaptive Immune ◽  
General Aspects ◽  
Inflammatory Molecules ◽  
The Impact

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades the host’s cells via the angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). ACE2 and TMPRSS2 molecules are highly expressed on the respiratory tract but are also expressed in other organs such as kidneys, heart, and intestine, which could partially explain the multiple organ infection, damage, and failure. During the COVID-19 disease course, patients may develop a dysregulation in the immune response, with an exacerbated production of pro-inflammatory molecules and hypercoagulation, which can collaborate to the increase in tissue damage and death. This chapter will cover general aspects of the innate and adaptive immune response during COVID-19, the impact of comorbidities on the immune response to SARS-CoV-2, and the immune response generated by COVID-19 vaccines.

scholarly journals Mathematical Modeling Identifies the Role of Adaptive Immunity as a Key Controller of Respiratory Syncytial Virus (RSV) Titer in Cotton Rats

2018 ◽  
Author(s):  
Darren Wethington ◽  
Olivia Harder ◽  
Karthik Uppulury ◽  
William C. L. Stewart ◽  
Phylip Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Viral Titer ◽  
Vaccine Candidates ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Cotton Rats ◽  
Infected Cells ◽  
Syncytial Virus

AbstractRespiratory syncytial virus (RSV) is a common virus that can have varying effects ranging from mild cold-like symptoms to mortality depending on the age and immune status of the individual. We combined mathematical modeling using ordinary differential equations (ODEs) with measurement of RSV infection kinetics in primary well differentiated human airway epithelial (HAE) cultures in vitro and in immunocompetent and immunosuppressed cotton rats to glean mechanistic details that underlie RSV infection kinetics in the lung. Quantitative analysis of viral titer kinetics in our mathematical model showed that the elimination of infected cells by the adaptive immune response generates unique RSV titer kinetic features including a faster time scale of viral titer clearance than viral production, and a monotonic decrease in the peak RSV titer with decreasing inoculum dose. Parameter estimation in the ODE model using a non-linear mixed effects approach revealed a very low rate (average single cell lifetime > 10 days) of cell lysis by RSV before the adaptive immune response is initiated. Our model predicted negligible changes in the RSV titer kinetics on earlier days (< 5 d.p.i) but a slower decay in RSV titer in immunosuppressed cotton rats compared to that in non-suppressed cotton rats at later days (>5 d.p.i) in silico. These predictions were in excellent agreement with the experimental results. Our combined approach quantified the importance of the adaptive immune response in suppressing RSV infection in cotton rats, which could be useful in testing RSV vaccine candidates.ImportanceA major difficulty in developing vaccines against RSV infection is our rudimentary understanding of the mechanisms that underlie RSV infection. We addressed this challenge by developing a mechanistic computational model with predictive powers for describing RSV infection kinetics in cotton rats. The model was constructed synergistically with in vitro and in vivo measurements. The combined framework determined an important role for CD8+ T cells responses in reducing RSV titers in cotton rats. The framework can be used to design future experiments to elucidate mechanisms underlying RSV infection and test outcomes for potential vaccine candidates. In addition, estimation of the model parameters provides quantitative values for parameters of biological and clinical interest such as the replication rate of RSV, the death rate of infected cells, and the average number of new infections initiated by a single infected cell.

scholarly journals C3H Male Mice with Severe Combined Immunodeficiency Cannot Clear a Urethral Infection with a Human Serovar of Chlamydia trachomatis

2009 ◽  
Vol 77 (12) ◽  
pp. 5602-5607 ◽  
Author(s):  
Sukumar Pal ◽  
Annahita K. Sarcon ◽  
Luis M. de la Maza
Keyword(s):  
Immune Response ◽  
Chlamydia Trachomatis ◽  
Severe Combined Immunodeficiency ◽  
Adaptive Immune Response ◽  
Genitourinary Tract ◽  
Combined Immunodeficiency ◽  
Male Mice ◽  
Infectious Dose ◽  
Adaptive Immune ◽  
Cell Mediated Immune Response

ABSTRACT The pathogenesis of an infection of the male genitourinary tract of mice with a human serovar of Chlamydia trachomatis has not been characterized. To establish a new model, we inoculated C3H/HeN (H-2 k ) mice in the meatus urethra with C. trachomatis serovar D. To determine the 50% infectious dose (ID50), male mice were inoculated with doses ranging from 102 to 106 inclusion-forming units (IFU). The mice were euthanized 10 days post infection (p.i.), and the urethra, bladder, epididimydes, and testes were cultured for Chlamydia. Positive cultures were obtained from the urethra, urinary bladder, and epididimydes, and the ID50 was determined to be 5 × 104 IFU/mouse. Subsequently, to characterize the course of the infection, wild-type (WT) and C3H animals with severe combined immunodeficiency (SCID animals) were inoculated with 106 IFU/mouse (20 times the ID50). In the WT mice, the infection peaked in the second week, and by 42 days p.i., it was cleared. In contrast, most of the SCID mice continued to have positive cultures at 60 days p.i. C. trachomatis-specific antibodies were first detected in WT animals' sera at 21 days p.i. and increased until 42 days p.i. The immunoglobulin G2a (IgG2a) titers were 32-fold higher than those of IgG1, indicative of a Th1-biased immune response. A lymphoproliferative assay using splenocytes showed a significant cell-mediated immune response in the WT mice. As expected, no humoral or cell-mediated immune responses were observed in the SCID animals. In conclusion, inoculation of WT male mice in the meatus urethra with a human serovar of C. trachomatis resulted in a limited infection mainly localized to the lower genitourinary tract. On the other hand, SCID animals could not clear the infection, suggesting that in male mice, the adaptive immune response is necessary to control an infection with a C. trachomatis human serovar.

scholarly journals The Paradox of a Phagosomal Lifestyle: How Innate Host Cell-Leishmania amazonensis Interactions Lead to a Progressive Chronic Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Matheus B. Carneiro ◽  
Nathan C. Peters
Keyword(s):  
Immune Response ◽  
Chronic Disease ◽  
Host Cell ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Leishmania Amazonensis ◽  
Host Cells ◽  
Adaptive Immune ◽  
Th2 Immunity ◽  
The Impact

Intracellular phagosomal pathogens represent a formidable challenge for innate immune cells, as, paradoxically, these phagocytic cells can act as both host cells that support pathogen replication and, when properly activated, are the critical cells that mediate pathogen elimination. Infection by parasites of the Leishmania genus provides an excellent model organism to investigate this complex host-pathogen interaction. In this review we focus on the dynamics of Leishmania amazonensis infection and the host innate immune response, including the impact of the adaptive immune response on phagocytic host cell recruitment and activation. L. amazonensis infection represents an important public health problem in South America where, distinct from other Leishmania parasites, it has been associated with all three clinical forms of leishmaniasis in humans: cutaneous, muco-cutaneous and visceral. Experimental observations demonstrate that most experimental mouse strains are susceptible to L. amazonensis infection, including the C57BL/6 mouse, which is resistant to other species such as Leishmania major, Leishmania braziliensis and Leishmania infantum. In general, the CD4+ T helper (Th)1/Th2 paradigm does not sufficiently explain the progressive chronic disease established by L. amazonensis, as strong cell-mediated Th1 immunity, or a lack of Th2 immunity, does not provide protection as would be predicted. Recent findings in which the balance between Th1/Th2 immunity was found to influence permissive host cell availability via recruitment of inflammatory monocytes has also added to the complexity of the Th1/Th2 paradigm. In this review we discuss the roles played by innate cells starting from parasite recognition through to priming of the adaptive immune response. We highlight the relative importance of neutrophils, monocytes, dendritic cells and resident macrophages for the establishment and progressive nature of disease following L. amazonensis infection.

Impact of adaptive immune response and cellular infection on delayed virus dynamics with multi-stages of infected cells

2019 ◽  
Vol 13 (01) ◽  
pp. 2050003
Author(s):  
A. M. Elaiw ◽  
N. H. AlShamrani
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Time Delays ◽  
Adaptive Immune Response ◽  
Virus Dynamics ◽  
Nonlinear Functions ◽  
Dynamics Model ◽  
Adaptive Immune ◽  
Infected Cells ◽  
Theoretical Results

In this investigation, we propose and analyze a virus dynamics model with multi-stages of infected cells. The model incorporates the effect of both humoral and cell-mediated immune responses. We consider two modes of transmissions, virus-to-cell and cell-to-cell. Multiple intracellular discrete-time delays have been integrated into the model. The incidence rate of infection as well as the generation and removal rates of all compartments are described by general nonlinear functions. We derive five threshold parameters which determine the existence of the equilibria of the model under consideration. A set of conditions on the general functions has been established which is sufficient to investigate the global stability of the five equilibria of the model. The global asymptotic stability of all equilibria is proven by utilizing Lyapunov function and LaSalle’s invariance principle. The theoretical results are illustrated by numerical simulations of the model with specific forms of the general functions.

The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection

2021 ◽  
Vol 41 (11) ◽  
pp. 407-414
Author(s):  
Michelle Møhlenberg ◽  
Ida Monrad ◽  
Line K. Vibholm ◽  
Stine S.F. Nielsen ◽  
Giacomo Schmidt Frattari ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
The Impact

scholarly journals Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia

2017 ◽  
Vol 91 (13) ◽  
Author(s):  
Daniel B. Reeves ◽  
Christopher W. Peterson ◽  
Hans-Peter Kiem ◽  
Joshua T. Schiffer
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Primary Infection ◽  
Adaptive Immune Response ◽  
Treatment Interruption ◽  
Viral Loads ◽  
Adaptive Immune ◽  
The Impact

ABSTRACT Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the “Berlin patient” remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation.

scholarly journals Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Martin Kongsbak-Wismann ◽  
Fatima A. H. Al-Jaberi ◽  
Jonas Damgård Schmidt ◽  
Mustafa Ghanizada ◽  
Cecilie Bo Hansen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
General Population ◽  
Vitamin D Receptor ◽  
Adaptive Immune Response ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Vitamin D Signaling ◽  
The Impact

The coronavirus disease 2019 (COVID-19) pandemic has severely impacted daily life all over the world. Any measures to slow down the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease disease severity are highly requested. Recent studies have reported inverse correlations between plasma levels of vitamin D and susceptibility to SARS-CoV-2 infection and COVID-19 severity. Therefore, it has been proposed to supplement the general population with vitamin D to reduce the impact of COVID-19. However, by studying the course of COVID-19 and the immune response against SARS-CoV-2 in a family with a mutated, non-functional vitamin D receptor, we here demonstrate that vitamin D signaling was dispensable for mounting an efficient adaptive immune response against SARS-CoV-2 in this family. Although these observations might not directly be transferred to the general population, they question a central role of vitamin D in the generation of adaptive immunity against SARS-CoV-2.

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