Research

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17 pages, 2798 KiB

Open AccessArticle

The Mathematical Modeling of the Host–Virus Interaction in Dengue Virus Infection: A Quantitative Study

by Zhaobin Xu, Hongmei Zhang, Dongying Yang, Dongqing Wei, Jacques Demongeot and Qiangcheng Zeng

Viruses 2024, 16(2), 216; https://doi.org/10.3390/v16020216 - 31 Jan 2024

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Abstract

Infectious diseases, such as Dengue fever, pose a significant public health threat. Developing a reliable mathematical model plays a crucial role in quantitatively elucidating the kinetic characteristics of antibody–virus interactions. By integrating previous models and incorporating the antibody dynamic theory, we have constructed [...] Read more.

Infectious diseases, such as Dengue fever, pose a significant public health threat. Developing a reliable mathematical model plays a crucial role in quantitatively elucidating the kinetic characteristics of antibody–virus interactions. By integrating previous models and incorporating the antibody dynamic theory, we have constructed a novel and robust model that can accurately simulate the dynamics of antibodies and viruses based on a comprehensive understanding of immunology principles. It explicitly formulates the viral clearance effect of antibodies, along with the positive feedback stimulation of virus–antibody complexes on antibody regeneration. In addition to providing quantitative insights into the dynamics of antibodies and viruses, the model exhibits a high degree of accuracy in capturing the kinetics of viruses and antibodies in Dengue fever patients. This model offers a valuable solution to modeling the differences between primary and secondary Dengue infections concerning IgM/IgG antibodies. Furthermore, it demonstrates that a faster removal rate of antibody–virus complexes might lead to a higher peak viral loading and worse clinical symptom. Moreover, it provides a reasonable explanation for the antibody-dependent enhancement of heterogeneous Dengue infections. Ultimately, this model serves as a foundation for constructing an optimal mathematical model to combat various infectious diseases in the future. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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23 pages, 4404 KiB

Open AccessArticle

Revealing Novel-Strain-Specific and Shared Epitopes of Infectious Bronchitis Virus Spike Glycoprotein Using Chemical Linkage of Peptides onto Scaffolds Precision Epitope Mapping

by Samantha Sives, Sarah Keep, Erica Bickerton and Lonneke Vervelde

Viruses 2023, 15(11), 2279; https://doi.org/10.3390/v15112279 - 20 Nov 2023

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Abstract

The avian coronavirus, infectious bronchitis virus (IBV), is an economically important infectious disease affecting chickens, with a diverse range of serotypes found globally. The major surface protein, spike (S), has high diversity between serotypes, and amino acid differences in the S1 sub-unit are [...] Read more.

The avian coronavirus, infectious bronchitis virus (IBV), is an economically important infectious disease affecting chickens, with a diverse range of serotypes found globally. The major surface protein, spike (S), has high diversity between serotypes, and amino acid differences in the S1 sub-unit are thought to be responsible for poor cross-protection afforded by vaccination. Here, we attempt to address this, by using epitope mapping technology to identify shared and serotype-specific immunogenic epitopes of the S glycoprotein of three major circulating strains of IBV, M41, QX, and 4/91, via CLIPS peptide arrays based on peptides from the S1 sub-units. The arrays were screened with sera from chickens immunised with recombinant IBV, based on Beau-R backbone expressing heterologous S, generated in two independent vaccination/challenge trials. The screening of sera from rIBV vaccination experiments led to the identification of 52 immunogenic epitopes on the S1 of M41, QX, and 4/91. The epitopes were assigned into six overlapping epitope binding regions. Based on accessibility and location in the hypervariable regions of S, three sequences, ²⁵YVYYYQSAFRPPNGWHLQGGAYAVVNSTN⁵⁴, ⁶⁷TVGVIKDVYNQSVASI⁸², and ⁸³AMTVPPAGMSWSVS⁹⁶, were selected for further investigation, and synthetic peptide mimics were recognised by polyclonal sera. These epitopes may have the potential to contribute towards a broader cross-protective IBV vaccine. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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11 pages, 2197 KiB

Open AccessArticle

Presence and Persistence of Andes Virus RNA in Human Semen

by Roland Züst, Rahel Ackermann-Gäumann, Nicole Liechti, Denise Siegrist, Sarah Ryter, Jasmine Portmann, Nicole Lenz, Christian Beuret, Roger Koller, Cornelia Staehelin, Andrea B. Kuenzli, Jonas Marschall, Sylvia Rothenberger and Olivier Engler

Viruses 2023, 15(11), 2266; https://doi.org/10.3390/v15112266 - 17 Nov 2023

Cited by 1 | Viewed by 1075

Abstract

When infecting humans, Andes orthohantavirus (ANDV) may cause a severe disease called hantavirus cardiopulmonary syndrome (HCPS). Following non-specific symptoms, the infection may progress to a syndrome of hemorrhagic fever combined with hyper-acute cardiopulmonary failure. The case fatality rate ranges between 25–40%, depending on [...] Read more.

When infecting humans, Andes orthohantavirus (ANDV) may cause a severe disease called hantavirus cardiopulmonary syndrome (HCPS). Following non-specific symptoms, the infection may progress to a syndrome of hemorrhagic fever combined with hyper-acute cardiopulmonary failure. The case fatality rate ranges between 25–40%, depending on the outbreak. In this study, we present the follow-up of a male patient who recovered from HCPS six years ago. We demonstrate that the ANDV genome persists within the reproductive tract for at least 71 months. Genome sequence analysis early and late after infection reveals a low number of mutations (two single nucleotide variants and one deletion), suggesting limited replication activity. We can exclude the integration of the viral genome into the host genome, since the treatment of the specimen with RNAse led to a loss of signal. We demonstrate a long-lasting, strong neutralizing antibody response using pseudovirions expressing the ANDV glycoprotein. Taken together, our results show that ANDV has the potential for sexual transmission. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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18 pages, 1909 KiB

Open AccessArticle

Higher HIV-1 Env gp120-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity Is Associated with Lower Levels of Defective HIV-1 Provirus

by Ryan Yucha, Morgan L. Litchford, Carolyn S. Fish, Zak A. Yaffe, Barbra A. Richardson, Elizabeth Maleche-Obimbo, Grace John-Stewart, Dalton Wamalwa, Julie Overbaugh and Dara A. Lehman

Viruses 2023, 15(10), 2055; https://doi.org/10.3390/v15102055 - 06 Oct 2023

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Abstract

A cure for HIV-1 (HIV) remains unrealized due to a reservoir of latently infected cells that persist during antiretroviral therapy (ART), with reservoir size associated with adverse health outcomes and inversely with time to viral rebound upon ART cessation. Once established during ART, [...] Read more.

A cure for HIV-1 (HIV) remains unrealized due to a reservoir of latently infected cells that persist during antiretroviral therapy (ART), with reservoir size associated with adverse health outcomes and inversely with time to viral rebound upon ART cessation. Once established during ART, the HIV reservoir decays minimally over time; thus, understanding factors that impact the size of the HIV reservoir near its establishment is key to improving the health of people living with HIV and for the development of novel cure strategies. Yet, to date, few correlates of HIV reservoir size have been identified, particularly in pediatric populations. Here, we employed a cross-subtype intact proviral DNA assay (CS-IPDA) to quantify HIV provirus between one- and two-years post-ART initiation in a cohort of Kenyan children (n = 72), which had a median of 99 intact (range: 0–2469), 1340 defective (range: 172–3.84 × 10⁴), and 1729 total (range: 178–5.11 × 10⁴) HIV proviral copies per one million T cells. Additionally, pre-ART plasma was tested for HIV Env-specific antibody-dependent cellular cytotoxicity (ADCC) activity. We found that pre-ART gp120-specific ADCC activity inversely correlated with defective provirus levels (n = 68, r = −0.285, p = 0.0214) but not the intact reservoir (n = 68, r = −0.0321, p-value = 0.800). Pre-ART gp41-specific ADCC did not significantly correlate with either proviral population (n = 68; intact: r = −0.0512, p-value = 0.686; defective: r = −0.109, p-value = 0.389). This suggests specific host immune factors prior to ART initiation can impact proviruses that persist during ART. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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14 pages, 2322 KiB

Open AccessArticle

B-Cell Epitopes-Based Chimeric Protein from SARS-CoV-2 N and S Proteins Is Recognized by Specific Antibodies in Serum and Urine Samples from Patients

by Fernanda F. Ramos, Isabela A. G. Pereira, Mariana M. Cardoso, Raquel S. Bandeira, Daniela P. Lage, Rahisa Scussel, Rafaela S. Anastacio, Victor G. Freire, Marina F. N. Melo, Joao A. Oliveira-da-Silva, Vivian T. Martins, Grasiele S. V. Tavares, Danniele L. Vale, Camila S. Freitas, Ana Thereza Chaves, Júlia F. M. Caporali, Paula F. Vassallo, Cecilia G. Ravetti, Vandack Nobre, Flavio G. Fonseca, Myron Christodoulides, Ricardo A. Machado-de-Ávila, Eduardo A. F. Coelho and Fernanda Ludolf Show full author list Hide full author list

Viruses 2023, 15(9), 1877; https://doi.org/10.3390/v15091877 - 05 Sep 2023

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Abstract

The impact of the COVID-19 pandemic caused by the SARS-CoV-2 virus underscored the crucial role of laboratorial tests as a strategy to control the disease, mainly to indicate the presence of specific antibodies in human samples from infected patients. Therefore, suitable recombinant antigens [...] Read more.

The impact of the COVID-19 pandemic caused by the SARS-CoV-2 virus underscored the crucial role of laboratorial tests as a strategy to control the disease, mainly to indicate the presence of specific antibodies in human samples from infected patients. Therefore, suitable recombinant antigens are relevant for the development of reliable tests, and so far, single recombinant proteins have been used. In this context, B-cell epitopes-based chimeric proteins can be an alternative to obtain tests with high accuracy through easier and cheaper production. The present study used bioinformatics tools to select specific B-cell epitopes from the spike (S) and the nucleocapsid (N) proteins from the SARS-CoV-2 virus, aiming to produce a novel recombinant chimeric antigen (N4S11-SC2). Eleven S and four N-derived B-cell epitopes were predicted and used to construct the N4S11-SC2 protein, which was analyzed in a recombinant format against serum and urine samples, by means of an in house-ELISA. Specific antibodies were detected in the serum and urine samples of COVID-19 patients, which were previously confirmed by qRT-PCR. Results showed that N4S11-SC2 presented 83.7% sensitivity and 100% specificity when using sera samples, and 91.1% sensitivity and 100% specificity using urine samples. Comparable findings were achieved with paired urine samples when compared to N and S recombinant proteins expressed in prokaryotic systems. However, better results were reached for N4S11-SC2 in comparison to the S recombinant protein when using paired serum samples. Anti-N4S11-SC2 antibodies were not clearly identified in Janssen Ad26.COV2.S COVID-19-vaccinated subjects, using serum or paired urine samples. In conclusion, this study presents a new chimeric recombinant antigen expressed in a prokaryotic system that could be considered as an alternative diagnostic marker for the SARS-CoV-2 infection, with the potential benefits to be used on serum or urine from infected patients. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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12 pages, 1398 KiB

Open AccessArticle

Correlation between Clinical Characteristics and Antibody Levels in COVID-19 Convalescent Plasma Donor Candidates

by Günalp Uzun, Rebecca Müller, Karina Althaus, Matthias Becker, Patrick Marsall, Daniel Junker, Stefanie Nowak-Harnau, Nicole Schneiderhan-Marra, Harald Klüter, Hubert Schrezenmeier, Peter Bugert and Tamam Bakchoul

Viruses 2023, 15(6), 1357; https://doi.org/10.3390/v15061357 - 12 Jun 2023

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Abstract

COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the [...] Read more.

COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the study. Clinical parameters were recorded and anti-SARS-CoV-2 antibody levels (Spike Trimer, Receptor Binding Domain (RBD), S1, S2 and nucleocapsid protein) as well as ACE2 binding inhibition were measured. An ACE2 binding inhibition < 20% was defined as an inadequate neutralization capacity. Univariate and multivariable logistic regression analysis was used to detect the predictors of inadequate neutralization capacity. Ninety-one CCP donors (56 female; 61%) were analyzed. A robust correlation between all SARS-CoV-2 IgG antibodies and ACE2 binding inhibition, as well as a positive correlation between donor age, body mass index, and a negative correlation between time since symptom onset and antibody levels were found. We identified time since symptom onset, normal body mass index (BMI), and the absence of high fever as independent predictors of inadequate neutralization capacity. Gender, duration of symptoms, and number of symptoms were not associated with SARS-CoV-2 IgG antibody levels or neutralization. Neutralizing capacity was correlated with SARS-CoV-2 IgG antibodies and associated with time since symptom onset, BMI, and fever. These clinical parameters can be easily incorporated into the preselection of CCP donors. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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Review

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32 pages, 2115 KiB

Open AccessReview

The Adaptive Immune Response against Bunyavirales

by Reem Alatrash and Bobby Brooke Herrera

Viruses 2024, 16(3), 483; https://doi.org/10.3390/v16030483 - 21 Mar 2024

Viewed by 1161

Abstract

The Bunyavirales order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection [...] Read more.

The Bunyavirales order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection in humans can be asymptomatic, or it may present with a range of conditions from a mild, febrile illness to severe hemorrhagic syndromes and/or neurological complications. There is a need to develop safe and effective vaccines, a process requiring better understanding of the adaptive immune responses involved during infection. This review highlights the most recent findings regarding T cell and antibody responses to the five Bunyavirales families with known human pathogens (Peribunyaviridae, Phenuiviridae, Hantaviridae, Nairoviridae, and Arenaviridae). Future studies that define and characterize mechanistic correlates of protection against Bunyavirales infections or disease will help inform the development of effective vaccines. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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14 pages, 1007 KiB

Open AccessReview

Insights from Avian Influenza: A Review of Its Multifaceted Nature and Future Pandemic Preparedness

by Jianning He and Yiu-Wing Kam

Viruses 2024, 16(3), 458; https://doi.org/10.3390/v16030458 - 17 Mar 2024

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Abstract

Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related [...] Read more.

Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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20 pages, 1077 KiB

Open AccessReview

Antibody-Dependent Enhancement with a Focus on SARS-CoV-2 and Anti-Glycan Antibodies

by Marina M. Ziganshina, Nadezhda V. Shilova, Eugenia O. Khalturina, Natalya V. Dolgushina, Sergey V. Borisevich, Ekaterina L. Yarotskaya, Nicolai V. Bovin and Gennady T. Sukhikh

Viruses 2023, 15(7), 1584; https://doi.org/10.3390/v15071584 - 20 Jul 2023

Cited by 1 | Viewed by 1683

Abstract

Antibody-dependent enhancement (ADE) is a phenomenon where virus-specific antibodies paradoxically cause enhanced viral replication and/or excessive immune responses, leading to infection exacerbation, tissue damage, and multiple organ failure. ADE has been observed in many viral infections and is supposed to complicate the course [...] Read more.

Antibody-dependent enhancement (ADE) is a phenomenon where virus-specific antibodies paradoxically cause enhanced viral replication and/or excessive immune responses, leading to infection exacerbation, tissue damage, and multiple organ failure. ADE has been observed in many viral infections and is supposed to complicate the course of COVID-19. However, the evidence is insufficient. Since no specific laboratory markers have been described, the prediction and confirmation of ADE are very challenging. The only possible predictor is the presence of already existing (after previous infection) antibodies that can bind to viral epitopes and promote the disease enhancement. At the same time, the virus-specific antibodies are also a part of immune response against a pathogen. These opposite effects of antibodies make ADE research controversial. The assignment of immunoglobulins to ADE-associated or virus neutralizing is based on their affinity, avidity, and content in blood. However, these criteria are not clearly defined. Another debatable issue (rather terminological, but no less important) is that in most publications about ADE, all immunoglobulins produced by the immune system against pathogens are qualified as pre-existing antibodies, thus ignoring the conventional use of this term for natural antibodies produced without any stimulation by pathogens. Anti-glycan antibodies (AGA) make up a significant part of the natural immunoglobulins pool, and there is some evidence of their antiviral effect, particularly in COVID-19. AGA have been shown to be involved in ADE in bacterial infections, but their role in the development of ADE in viral infections has not been studied. This review focuses on pros and cons for AGA as an ADE trigger. We also present the results of our pilot studies, suggesting that AGAs, which bind to complex epitopes (glycan plus something else in tight proximity), may be involved in the development of the ADE phenomenon. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response, 2nd Edition)

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