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Host Immune Responses to RNA Viruses

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A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 30506

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Dr. Stephanie Longet

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Guest Editor

International Center for Infectiology Research—INSERM, GIMAP—University of Saint-Etienne,10 rue de la Marandière, 42270 Saint-Priest-en-Jarez, France
Interests: antibody response; adaptive immune response; viral antibody; vaccine antibody; SARS-CoV-2; Ebola virus; Lassa virus; mucosal immune response
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Prof. Dr. Miles Carroll

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Guest Editor

Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford 5OX3 7BN, UK
Interests: emerging diseases; adaptive immune response; neutralising response; Ebola virus; Marburg virus; Lassa virus; human coronaviruses; Crimean–Congo haemorrhagic fever; vaccine-induced immune response; sero-epidemiology; immune evasion
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

RNA viruses have the ability to infect bacteria, plants, animals and humans. Over the past century, infections due to RNA viruses including human immunodeficiency virus 1 (HIV-1), influenza virus, rotavirus, West Nile virus, Dengue virus, and measles virus have been major threats to human health. Furthermore, RNA viruses are often the cause of emerging infectious diseases in humans with high consequences on healthcare systems and economy. Some examples of RNA viruses which have caused emerging diseases are severe acute respiratory syndrome related (SARS) coronavirus, Middle East respiratory syndrome (MERS) coronavirus, and the Ebola virus. The huge global impact of SARS-CoV-2 which emerged in 2019 highlighted the importance of preparedness to fight RNA viruses. A better understanding of host immune responses to RNA viruses is a key aspect to define correlates of protection essential to improve or develop therapeutic strategies and vaccine platforms.

A lot of effort has been put into research on RNA viruses including Poliovirus, HIV-1, and influenza virus for many years, but other RNA viruses including Chikungunya, Zika, and Nipah viruses have the potential to become epidemics. Recent advancements in the characterisation of protective immune response to some RNA viruses, such as Ebola virus or SARS-CoV-2, quickly led to first-generation vaccine development. However, knowledge gaps in host immune responses to a number of RNA viruses still exist. Host-immune factors leading to the control of infection as well as immune determinants involved in disease severity, or latency and viral reservoir in particular cases, are not fully understood. In addition, RNA viruses may show a high mutation rate in their host due to the lack of proofreading by their replicases, which can lead to immune evasion. Immune mechanisms against viral evasion are not fully defined. Such information will be crucial to design novel vaccine and therapeutic strategies.

I would like to invite colleagues investigating immune responses to any of the RNA viruses in in vitro or ex vivo models, animal models or humans within the area of immunology, virology, public health and epidemiology to submit their manuscripts to this Special Issue of Pathogens in the form of original research and reviews. Potential topics include but are not limited to:

Characterisation of humoral and cellular responses during RNA virus infections;
Dynamics of innate immune response to RNA virus infection;
Role of host immune responses in pathogenesis of viral infections;
Immune mechanisms against viral escape.

Dr. Stephanie Longet
Prof. Dr. Miles Carroll
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

RNA viruses
antibody response
cellular response
innate response
immune evasion
viral infections
memory response
correlates of protection
protective response
humans
animal models
public health

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Related Special Issue

Host Immune Responses to RNA Viruses, 2nd Edition in Pathogens (8 articles)

Published Papers (9 papers)

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Research

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14 pages, 1975 KiB

Open AccessArticle

The Involvement of Neutrophil in the Immune Dysfunction Associated with BVDV Infection

by Karim Abdelsalam, Radhey S Kaushik and Christopher Chase

Pathogens 2023, 12(5), 737; https://doi.org/10.3390/pathogens12050737 - 20 May 2023

Cited by 2 | Viewed by 1521

Abstract

Bovine viral diarrhea virus (BVDV) induces immune dysfunction that often results in a secondary bacterial infection in the infected animals. The underlying mechanism of BVDV-induced immune dysfunction is not well understood. The role of BVDV-infected macrophage-secreted factors was investigated. BVDV-infected monocyte-derived macrophage (MDM) supernatants down-regulated the expression of neutrophil L-selectin and CD18. Regardless of the biotype, phagocytic activity and oxidative burst were downregulated by BVDV-infected MDM supernatants. However, only supernatants from cytopathic (cp) BVDV down-regulated nitric oxide production and neutrophil extracellular traps (NET) induction. Our data suggested that BVDV-induced macrophage-secreted factors caused immune dysfunction in neutrophils. Unlike lymphocyte depletion, the negative impact on neutrophils seems to be specific to cp BVDV biotype. Interestingly the majority of modified live BVDV vaccines are based on cp strain of BVDV. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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17 pages, 3061 KiB

Open AccessArticle

Infection with Seasonal H1N1 Influenza Results in Comparable Disease Kinetics and Host Immune Responses in Ferrets and Golden Syrian Hamsters

by Jemma Paterson, Kathryn A. Ryan, Daniel Morley, Nicola J. Jones, Paul Yeates, Yper Hall, Catherine J. Whittaker, Francisco J. Salguero and Anthony C. Marriott

Pathogens 2023, 12(5), 668; https://doi.org/10.3390/pathogens12050668 - 30 Apr 2023

Cited by 3 | Viewed by 2000

Abstract

Animal models of influenza are important in preclinical research for the study of influenza infection and the assessment of vaccines, drugs and therapeutics. Here, we show that Golden Syrian hamsters (Mesocricetus auratus) inoculated via the intranasal route with high dose of influenza H1N1 display comparable disease kinetics and immune responses to the ‘gold standard’ ferret (Mustela furo) model. We demonstrate that both the hamster and ferret models have measurable disease endpoints of weight loss, temperature change, viral shedding from the upper respiratory tract and increased lung pathology. We also characterised both the humoral and cellular immune responses to infection in both models. The comparability of these data supports the Golden Syrian hamster model being useful in preclinical evaluation studies to explore the efficacy of countermeasures against influenza. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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19 pages, 5580 KiB

Open AccessArticle

HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus

by Xinlian Zhang, Savitha Deshmukh, Amey Mukim, Jasen Zhang and Nadejda Beliakova-Bethell

Pathogens 2023, 12(4), 511; https://doi.org/10.3390/pathogens12040511 - 24 Mar 2023

Cited by 2 | Viewed by 1877

Abstract

Identification of a cellular biomarker of latent HIV infection will facilitate the latent reservoir detection, quantification, and targeting for elimination. Unfortunately, the latency biomarkers reported in the literature define only a fraction of the entire reservoir. The latent HIV reservoir may be established in dividing cells that subsequently return to quiescence and in resting cells. The strength of the T cell receptor (TCR) signaling at the time of infection affects characteristics of the established reservoir, such as the ability to reactivate with latency reversing agents. To better understand the cellular environments before latency establishment, we characterized transcriptomic remodeling induced by the initial HIV infection in cells with differential proliferative responses to the TCR stimulus. Cell proliferation was monitored using the viable dye carboxyfluorescein diacetate succinimidyl ester. Cells that divided many times, a few times, or remained non-dividing were subjected to single-cell RNA sequencing. A subset of identified transcriptional changes induced by HIV infection was independent of the number of cell divisions; however, responses unique to different cell subsets were also detected. Some of these early gene expression changes were consistent with reported markers of latently infected cells. We pose that the latency biomarkers may depend on the cellular proliferative state at the time of infection. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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12 pages, 901 KiB

Open AccessArticle

Cellular Immune Profiling of Lung and Blood Compartments in Patients with SARS-CoV-2 Infection

by Letizia Santinelli, Alessandro Lazzaro, Francesca Sciarra, Luca Maddaloni, Federica Frasca, Matteo Fracella, Sonia Moretti, Alessandra Borsetti, Ginevra Bugani, Francesco Alessandri, Veronica Zullino, Franco Ruberto, Francesco Pugliese, Leonardo Sorrentino, Daniele Gianfrilli, Andrea Isidori, Mary Anna Venneri, Claudio M. Mastroianni, Giancarlo Ceccarelli and Gabriella d’Ettorre

Pathogens 2023, 12(3), 442; https://doi.org/10.3390/pathogens12030442 - 11 Mar 2023

Cited by 3 | Viewed by 2192

Abstract

Background: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19. Methods: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56^bright and CD56^dim), as well as CD4⁺ and CD8⁺ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry. Results: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors (p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients (p > 0.05). The only exception was for peripheral naïve CD4⁺ T cells levels that were reduced in non-survivors (p = 0.04). An increase in the levels of CD56^bright (p = 0.012) and a decrease in CD56^dim (p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4⁺ and CD8⁺ T cell levels in the lung compartment were lower compared to blood (p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4⁺ and CD8⁺ T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 (p < 0.05). Conclusions: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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14 pages, 2124 KiB

Open AccessArticle

The Efficient Antiviral Response of A549 Cells Is Enhanced When Mitochondrial Respiration Is Promoted

by Grégorie Lebeau, Daed El Safadi, Aurélie Paulo-Ramos, Mathilde Hoareau, Philippe Desprès, Pascale Krejbich-Trotot, Florian Chouchou, Marjolaine Roche and Wildriss Viranaicken

Pathogens 2022, 11(10), 1168; https://doi.org/10.3390/pathogens11101168 - 11 Oct 2022

Cited by 4 | Viewed by 2695

Abstract

When exposed to a viral infection, the attacked cells promptly set up defense mechanisms. As part of the antiviral responses, the innate immune interferon pathway and associated interferon-stimulated genes notably allow the production of proteins bearing antiviral activity. Numerous viruses are able to evade the interferon response, highlighting the importance of controlling this pathway to ensure their efficient replication. Several viruses are also known to manipulate the metabolism of infected cells to optimize the availability of amino acids, nucleotides, and lipids. They then benefit from a reprogramming of the metabolism that favors glycolysis instead of mitochondrial respiration. Given the increasingly discussed crosstalk between metabolism and innate immunity, we wondered whether this switch from glycolysis to mitochondrial respiration would be beneficial or deleterious for an efficient antiviral response. We used a cell-based model of metabolic reprogramming. Interestingly, we showed that increased mitochondrial respiration was associated with an enhanced interferon response following polyriboinosinic:polyribocytidylic acid (poly:IC) stimulation. This suggests that during viral infection, the metabolic reprogramming towards glycolysis is also part of the virus’ strategies to inhibit the antiviral response. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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Review

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17 pages, 580 KiB

Open AccessReview

The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections

by Alaa Elsaghir, Ehsan M. W. El-Sabaa, Abdulrahman K. Ahmed, Sayed F. Abdelwahab, Ibrahim M. Sayed and Mohamed A. El-Mokhtar

Pathogens 2023, 12(2), 279; https://doi.org/10.3390/pathogens12020279 - 8 Feb 2023

Cited by 8 | Viewed by 3862

Abstract

CD39 is a marker of immune cells such as lymphocytes and monocytes. The CD39/CD73 pathway hydrolyzes ATP into adenosine, which has a potent immunosuppressive effect. CD39 regulates the function of a variety of immunologic cells through the purinergic signaling pathways. CD39+ T cells have been implicated in viral infections, including Human Immunodeficiency Virus (HIV), Cytomegalovirus (CMV), viral hepatitis, and Corona Virus Disease 2019 (COVID-19) infections. The expression of CD39 is an indicator of lymphocyte exhaustion, which develops during chronicity. During RNA viral infections, the CD39 marker can profile the populations of CD4+ T lymphocytes into two populations, T-effector lymphocytes, and T-regulatory lymphocytes, where CD39 is predominantly expressed on the T-regulatory cells. The level of CD39 in T lymphocytes can predict the disease progression, antiviral immune responses, and the response to antiviral drugs. Besides, the percentage of CD39 and CD73 in B lymphocytes and monocytes can affect the status of viral infections. In this review, we investigate the impact of CD39 and CD39-expressing cells on viral infections and how the frequency and percentage of CD39+ immunologic cells determine disease prognosis. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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25 pages, 1993 KiB

Open AccessEditor’s ChoiceReview

Endogenous Retroviruses as Modulators of Innate Immunity

by Eric Russ and Sergey Iordanskiy

Pathogens 2023, 12(2), 162; https://doi.org/10.3390/pathogens12020162 - 19 Jan 2023

Cited by 24 | Viewed by 6658

Abstract

Endogenous retroviruses (ERVs), or LTR retrotransposons, are a class of transposable elements that are highly represented in mammalian genomes. Human ERVs (HERVs) make up roughly 8.3% of the genome and over the course of evolution, HERV elements underwent positive selection and accrued mutations that rendered them non-infectious; thereby, the genome could co-opt them into constructive roles with important biological functions. In the past two decades, with the help of advances in sequencing technology, ERVs are increasingly considered to be important components of the innate immune response. While typically silenced, expression of HERVs can be induced in response to traumatic, toxic, or infection-related stress, leading to a buildup of viral transcripts and under certain circumstances, proteins, including functionally active reverse transcriptase and viral envelopes. The biological activity of HERVs in the context of the innate immune response can be based on the functional effect of four major viral components: (1) HERV LTRs, (2) HERV-derived RNAs, (3) HERV-derived RNA:DNA duplexes and cDNA, and (4) HERV-derived proteins and ribonucleoprotein complexes. In this review, we will discuss the implications of HERVs in all four contexts in relation to innate immunity and their association with various pathological disease states. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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22 pages, 2150 KiB

Open AccessReview

Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies

by Marija Rozman, Snjezana Zidovec-Lepej, Karlo Jambrosic, Maja Babić and Irena Drmić Hofman

Pathogens 2023, 12(1), 92; https://doi.org/10.3390/pathogens12010092 - 5 Jan 2023

Cited by 9 | Viewed by 3665

Abstract

Toll-like receptors (TLRs), as a family of pattern recognition receptors, play an important role in the recognition of HIV-1 molecular structures by various cells of the innate immune system, but also provide a functional association with subsequent mechanisms of adaptive immunity. TLR7 and TLR8 play a particularly important role in the innate immune response to RNA viruses due to their ability to recognise GU-rich single-stranded RNA molecules and subsequently activate intracellular signalling pathways resulting in expression of genes coding for various biological response modifiers (interferons, proinflammatory cytokines, chemokines). The aim of this review is to summarise the most recent knowledge on the role of TLRs in the innate immune response to HIV-1 and the role of TLR gene polymorphisms in the biology and in the clinical aspects of HIV infections. In addition, the role of TLR agonists as latency reversing agents in research to treat HIV infections and as immunomodulators in HIV vaccine research will be discussed. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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42 pages, 2769 KiB

Open AccessReview

RNA Viruses, Pregnancy and Vaccination: Emerging Lessons from COVID-19 and Ebola Virus Disease

by Chandrasekharan Rajalekshmi Dhanya, Aswathy Shailaja, Aarcha Shanmugha Mary, Sumodan Padikkala Kandiyil, Ambili Savithri, Vishnu Sasidharan Lathakumari, Jayakrishnan Therthala Veettil, Jiji Joseph Vandanamthadathil and Maya Madhavan

Pathogens 2022, 11(7), 800; https://doi.org/10.3390/pathogens11070800 - 15 Jul 2022

Cited by 3 | Viewed by 4635

Abstract

Pathogenic viruses with an RNA genome represent a challenge for global human health since they have the tremendous potential to develop into devastating pandemics/epidemics. The management of the recent COVID-19 pandemic was possible to a certain extent only because of the strong foundations laid by the research on previous viral outbreaks, especially Ebola Virus Disease (EVD). A clear understanding of the mechanisms of the host immune response generated upon viral infections is a prime requisite for the development of new therapeutic strategies. Hence, we present here a comparative study of alterations in immune response upon SARS-CoV-2 and Ebola virus infections that illustrate many common features. Vaccination and pregnancy are two important aspects that need to be studied from an immunological perspective. So, we summarize the outcomes and immune responses in vaccinated and pregnant individuals in the context of COVID-19 and EVD. Considering the significance of immunomodulatory approaches in combating both these diseases, we have also presented the state of the art of such therapeutics and prophylactics. Currently, several vaccines against these viruses have been approved or are under clinical trials in various parts of the world. Therefore, we also recapitulate the latest developments in these which would inspire researchers to look for possibilities of developing vaccines against many other RNA viruses. We hope that the similar aspects in COVID-19 and EVD open up new avenues for the development of pan-viral therapies. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)

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