International Journal of Molecular Sciences

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18 pages, 9174 KB

Open AccessArticle

Evaluation of Systemic Injury in Calves with Rotavirus-Induced Diarrhea Using Sensitive Biomarkers and Immunopathology

by Murat Uztimür, Cennet Nur Ünal, Muhammet Bahaddin Dörtbudak, Davide Bisanti and Alessandro Di Cerbo

Int. J. Mol. Sci. 2026, 27(1), 65; https://doi.org/10.3390/ijms27010065 - 20 Dec 2025

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Abstract

Studies in human medicine have demonstrated that rotavirus infection can also affect extraintestinal sites due to its systemic effects. However, in veterinary medicine, the injury caused by rotavirus diarrhea is limited to the intestines, and its effects on various systemic structures remain poorly [...] Read more.

Studies in human medicine have demonstrated that rotavirus infection can also affect extraintestinal sites due to its systemic effects. However, in veterinary medicine, the injury caused by rotavirus diarrhea is limited to the intestines, and its effects on various systemic structures remain poorly understood. In this observational case–control study, we aimed to determine the effects of HSP-27, Caspase-3, IL-2, γ-H2AX, HMGB-1, SP-D, and GDH (or GLDH) on the pathogenesis of rotavirus infection by using biomarkers for diagnostic purposes in lung and liver injury in neonate diarrheic calves naturally infected with rotavirus, both alive and post-mortem. Fifty-two Simmental calves (1–28 days old) of both sexes, 40 infected with rotavirus and 12 healthy, were studied. Twenty-eight out of 40 survived, while the remainder underwent necropsy for histopathological and immunopathological (HSP-27, Caspase-3, IL-2, γ-H2AX) examination of the lungs and livers. Lung and liver-specific serum E-selectin, glutamate dehydrogenase, surfactant protein-D, and high mobility group box-1 were analyzed by a bovine-specific ELISA kit (Shanghai Coon Koon Biotech Co., Ltd., China). Histopathological and immunohistochemical analyses confirmed lung and liver injury in naturally infected calves. HMGB-1, SP-D, and GDH concentrations were significantly higher in naturally infected calves than in the control group (p < 0.001, p < 0.001, and p < 0.05, respectively), showing an excellent diagnostic predictive capacity for lung and liver injury. Also, IL-2, HSP-27, CASP-3, and γ-H2AX were significantly expressed in the lungs (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) and liver (p < 0.001, p < 0.001, p < 0.01, and p < 0.01, respectively). All these observations led us to hypothesize that oxidative stress, apoptosis, and DNA damage may underlie the pathogenesis of this condition. Nevertheless, further studies on large populations of rotavirus-infected calves are needed to confirm the data reported in the current study. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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14 pages, 4707 KB

Open AccessArticle

Cross-Reactive Immune Response of Bovine Coronavirus Spike Glycoprotein to SARS-CoV-2 Variants of Concern

by Chiara Cossu, Valentina Franceschi, Antonino Di Lorenzo, Elisabetta Bolli, Sergio Minesso, Camilla Cotti, Laura Conti and Gaetano Donofrio

Int. J. Mol. Sci. 2024, 25(21), 11509; https://doi.org/10.3390/ijms252111509 - 26 Oct 2024

Cited by 4 | Viewed by 2883

Abstract

The high variability observed in the clinical symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been attributed to the presence, in a proportion of infection-naive subjects, of pre-existing cross-reactive immune responses. Here, we demonstrate that the bovine coronavirus spike protein [...] Read more.

The high variability observed in the clinical symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been attributed to the presence, in a proportion of infection-naive subjects, of pre-existing cross-reactive immune responses. Here, we demonstrate that the bovine coronavirus spike protein (BoS) may represent a source of protective immunity to SARS-CoV-2. Indeed, vaccination of BALB/c mice with a Bovine herpesvirus 4 (BoHV-4)-based vector expressing BoS induced both cell-mediated and humoral immune responses that cross-react with SARS-CoV-2 spike protein. Although the spike-specific antibodies induced by BoS did not neutralize SARS-CoV-2, the T lymphocytes activated by BoS were able to induce cytotoxicity of cells expressing spike proteins derived from several SARS-CoV-2 variants. These results demonstrate that immunization with BoS may represent a source of cross-reactive immunity to SARS-CoV-2, and that these cross-reactive immune responses may exert protective functions. These results contribute to deciphering the mechanisms responsible for lack or mildness of symptoms observed in many individuals upon SARS-CoV-2 infection and may open new ways for the development of new vaccines for coronaviruses. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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18 pages, 3681 KB

Open AccessArticle

Post-Transcriptional Induction of the Antiviral Host Factor GILT/IFI30 by Interferon Gamma

by Taisuke Nakamura, Mai Izumida, Manya Bakatumana Hans, Shuichi Suzuki, Kensuke Takahashi, Hideki Hayashi, Koya Ariyoshi and Yoshinao Kubo

Int. J. Mol. Sci. 2024, 25(17), 9663; https://doi.org/10.3390/ijms25179663 - 6 Sep 2024

Cited by 3 | Viewed by 2330

Abstract

Gamma-interferon-inducible lysosomal thiol reductase (GILT) plays pivotal roles in both adaptive and innate immunities. GILT exhibits constitutive expression within antigen-presenting cells, whereas in other cell types, its expression is induced by interferon gamma (IFN-γ). Gaining insights into the precise molecular mechanism governing the [...] Read more.

Gamma-interferon-inducible lysosomal thiol reductase (GILT) plays pivotal roles in both adaptive and innate immunities. GILT exhibits constitutive expression within antigen-presenting cells, whereas in other cell types, its expression is induced by interferon gamma (IFN-γ). Gaining insights into the precise molecular mechanism governing the induction of GILT protein by IFN-γ is of paramount importance for adaptive and innate immunities. In this study, we found that the 5′ segment of GILT mRNA inhibited GILT protein expression regardless of the presence of IFN-γ. Conversely, the 3′ segment of GILT mRNA suppressed GILT protein expression in the absence of IFN-γ, but it loses this inhibitory effect in its presence. Although the mTOR inhibitor rapamycin suppressed the induction of GILT protein expression by IFN-γ, the expression from luciferase sequence containing the 3′ segment of GILT mRNA was resistant to rapamycin in the presence of IFN-γ, but not in its absence. Collectively, this study elucidates the mechanism behind GILT induction by IFN-γ: in the absence of IFN-γ, GILT mRNA is constitutively transcribed, but the translation process is hindered by both the 5′ and 3′ segments. Upon exposure to IFN-γ, a translation inhibitor bound to the 3′ segment is liberated, and a translation activator interacts with the 3′ segment to trigger the initiation of GILT translation. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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Review

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20 pages, 913 KB

Open AccessReview

Post-Translational Modifications in Respiratory Virus Infection: Recent Insights into the Development of In Vitro Models

by Emna Ben Khlifa, Alessia Campese, Andrea Corsi, Cristina Bombieri, Maria Grazia Romanelli, Maria Teresa Valenti, Donato Zipeto, Matteo Castelli, Patricia Marie-Jeanne Lievens and Alessandra Ruggiero

Int. J. Mol. Sci. 2025, 26(24), 12174; https://doi.org/10.3390/ijms262412174 - 18 Dec 2025

Cited by 2 | Viewed by 835

Abstract

Post-translational modifications (PTMs) are crucial chemical alterations occurring on proteins post-synthesis, impacting various cellular processes. During viral infections, PTMs are shown to play a multitude of roles in viral replication, host interaction, and immune evasion. Thus, these modifications can influence infectivity, with direct [...] Read more.

Post-translational modifications (PTMs) are crucial chemical alterations occurring on proteins post-synthesis, impacting various cellular processes. During viral infections, PTMs are shown to play a multitude of roles in viral replication, host interaction, and immune evasion. Thus, these modifications can influence infectivity, with direct impact on the anti-viral host immune responses and potentially viral adaptation across species. This field is still scarcely explored, whilst understanding PTMs is not only important to advance the knowledge of virus pathology but also potentially to provide insights for vaccine development. In this review, we attempt to summarize the latest findings mainly published over the last 10 years, focusing on the roles of PTMs involved in virus infection and anti-viral immune responses, in the context of relevant human respiratory infections: influenza A virus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2. We decided to concentrate on these three viruses because they currently represent a global health problem due to recurrent outbreaks and pandemic potential. A deeper characterization of the PTMs may help in understanding virus–host interaction with possible implications on curative strategies. Further, we will report on cutting-edge technologies to study in vitro virus infection in different cellular-based systems. In particular, we describe and discuss the application of 2D and 3D lung organoid cell-culture systems as in vitro models to mimic respiratory environments and to study the PTMs in a controlled setting. Finally, we will discuss the importance of PTMs in the context of next-generation vaccine design, especially for their potential role to offer effective protection against respiratory viruses. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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36 pages, 1641 KB

Open AccessReview

Advances in the Diagnosis and Treatment of Rotavirus Infections: Narrative Review

by Karolina Pawłuszkiewicz, Emilia Kucharczyk, Matylda Korgiel, Tomasz Busłowicz, Anita Faltus, Natalia Kucharczyk and Emil Paluch

Int. J. Mol. Sci. 2025, 26(18), 9175; https://doi.org/10.3390/ijms26189175 - 19 Sep 2025

Cited by 1 | Viewed by 6762

Abstract

Rotavirus remains one of the leading causes of severe gastroenteritis, particularly among infants and young children, despite the introduction of effective vaccines. Although the global burden of rotavirus-associated morbidity and mortality has decreased in recent years, significant challenges remain regarding accurate diagnosis, optimal [...] Read more.

Rotavirus remains one of the leading causes of severe gastroenteritis, particularly among infants and young children, despite the introduction of effective vaccines. Although the global burden of rotavirus-associated morbidity and mortality has decreased in recent years, significant challenges remain regarding accurate diagnosis, optimal clinical management, and equitable access to preventive measures. The aim of this narrative review is to provide a comprehensive synthesis of recent advances in the diagnosis and treatment of rotavirus infections. Particular emphasis is placed on post-guideline research emerging after the publication of the Evidence-Based Guidelines from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and the European Society for Pediatric Infectious Diseases (ESPID), offering updated perspectives on therapeutic strategies and clinical practices. In addition, this review discusses the expanding role of molecular diagnostic methods, which offer enhanced sensitivity and specificity in the detection of rotavirus, and evaluates novel antiviral agents under investigation. By integrating and analyzing the most relevant research published within the past decade, we aim to delineate key progress, identify persistent gaps in knowledge, and propose future directions for research and clinical application. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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16 pages, 1588 KB

Open AccessReview

The Role of Lactylation in Virus–Host Interactions

by Gejie Zhao, Jia Zhou, Shutong He, Xiao Fei and Guijie Guo

Int. J. Mol. Sci. 2025, 26(14), 6613; https://doi.org/10.3390/ijms26146613 - 10 Jul 2025

Cited by 2 | Viewed by 3171

Abstract

Lactylation, a novel form of post-translational modifications (PTMs) of protein, particularly within histone proteins, has recently gained attention for its role in regulating gene expression and cellular processes. In recent years, lactylation has been widely studied in cancer, immune diseases, neurological diseases, cardiovascular [...] Read more.

Lactylation, a novel form of post-translational modifications (PTMs) of protein, particularly within histone proteins, has recently gained attention for its role in regulating gene expression and cellular processes. In recent years, lactylation has been widely studied in cancer, immune diseases, neurological diseases, cardiovascular diseases, metabolic diseases, etc. Increasing evidence now suggests that lactylation also plays a significant role in the host’s innate immune response to viruses. Lactylation influences fundamental cellular functions, including transcriptional regulation, signal transduction, cell proliferation and differentiation. It affects protein behavior by modulating their function, stability, subcellular localization and interactions. Studies have shown that many viral infections promote lactate production through enhanced glycolysis, a process that facilitates viral replication. Given that innate immunity serves as the host’s first line of defense against pathogenic invasion, understanding how lactylation regulates antiviral responses offers promising avenues for the development of diagnostic tools and therapeutic strategies against viral diseases. In this review, we provide a comprehensive overview of recent research on the role of lactylation in viral–host interactions. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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13 pages, 794 KB

Open AccessReview

HIV-Associated Dermatological Alterations: Barrier Dysfunction, Immune Impairment, and Microbiome Changes

by Muhammad Anshory, Handono Kalim, Jan L. Nouwen and Hok Bing Thio

Int. J. Mol. Sci. 2025, 26(7), 3199; https://doi.org/10.3390/ijms26073199 - 30 Mar 2025

Cited by 2 | Viewed by 3129

Abstract

Human Immunodeficiency Virus (HIV) significantly impacts skin structure, immune responses, and the microbiome, contributing to diverse dermatological conditions. The epidermis, a key physical and immunological barrier, undergoes structural changes such as hyperplasia and inflammatory infiltrates. Skin adnexal structures like hair follicles also play [...] Read more.

Human Immunodeficiency Virus (HIV) significantly impacts skin structure, immune responses, and the microbiome, contributing to diverse dermatological conditions. The epidermis, a key physical and immunological barrier, undergoes structural changes such as hyperplasia and inflammatory infiltrates. Skin adnexal structures like hair follicles also play a role in immune modulation but are affected by HIV-related disruptions. Innate and adaptive immune systems are compromised due to CD4+ T-cell depletion, cytokine imbalances, and altered immune regulation, leading to conditions such as hypersensitivity and inflammatory dermatoses. The skin microbiome in HIV patients shows distinct shifts, including reduced Cutibacterium species and increased opportunistic microbes, independent of CD4+ levels. Age, sex, and environmental stressors exacerbate these changes, with women exhibiting stronger immune responses but higher risks of autoimmune diseases and aging men experiencing accelerated immunosenescence. Understanding these interconnected alterations is essential for developing targeted therapies to manage skin complications and improve the overall health of HIV patients. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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21 pages, 1708 KB

Open AccessReview

Exploring the Contrasts and Similarities of Dengue and SARS-CoV-2 Infections During the COVID-19 Era

by Alexis Hipólito García and Juan Bautista De Sanctis

Int. J. Mol. Sci. 2024, 25(21), 11624; https://doi.org/10.3390/ijms252111624 - 29 Oct 2024

Cited by 6 | Viewed by 4864

Abstract

Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only [...] Read more.

Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only a portion of the antibodies produced against SARS-CoV-2 proteins demonstrate neutralizing properties, and the immune response following natural infection tends to be temporary. In contrast, long-lasting IgG antibodies are common after dengue virus infections. In cases where preexisting antibodies from an initial dengue virus infection bind to a different dengue serotype during a subsequent infection, there is a potential for antibody-dependent enhancement (ADE) and the formation of immune complexes associated with disease severity. Both SARS-CoV-2 and dengue infections can result in immunodeficiency. Viral proteins of both viruses interfere with the host’s IFN-I signaling. Additionally, a cytokine storm can occur after viral infection, impairing a proper response, and autoantibodies against a wide array of proteins can appear during convalescence. Most of the reported autoantibodies are typically short-lived. Vaccines against both viruses alter the immune response, affecting the course of viral infection and enhancing clearance. A comprehensive analysis of both viral infections and pathogenicity is revisited to prevent infection, severity, and mortality. Full article

(This article belongs to the Special Issue Viral Infections and Immune Responses)

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