Virus Infection Research Articles

Risk factors for hepatocellular carcinoma in cirrhosis: A comprehensive analysis from a decade-long study

BACKGROUND Cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). Variability in HCC risk among patients with cirrhosis is notable, particularly when considering the diverse etiologies of cirrhosis. AIM To identify specific risk factors contributing to HCC development in patients with cirrhosis. METHODS This retrospective study analyzed data from cirrhotic patients at Beijing Youan Hospital from January 1, 2012 to September 30, 2022 with at least 6 mo of follow-up. Patient demographics, medical histories, etiologies, and clinical characteristics were examined. Cox regression analysis was used to analyze correlations of the above parameters with hepatocarcinogenesis, while competing risk regression was used to estimate their adjusted hazard ratios accounting for death. The cumulative incidence was plotted over time. RESULTS Overall, 5417 patients with cirrhosis (median age: 54 years; 65.8% males) were analyzed. Hepatitis B virus (HBV) was the most common etiology (23.3%), with 25% (n = 1352) developing HCC over a 2.9-year follow-up period. Patients with multiple etiologies had the HCC highest incidence (30.3%), followed by those with HBV-related cirrhosis (29.5%). Significant risk factors included male sex, advanced age, hepatitis C virus (HCV) infection, elevated blood ammonia, and low platelet count. Men had a higher 5-year HCC risk than women (37.0% vs 31.5%). HBV, HCV, and HBV/HCV co-infected patients had 5-year risks of HCC of 45.8%, 42.9%, and 48.1%, respectively, compared to 29.5% in nonviral hepatitis cases, highlighting the significant HCC risk from viral hepatitis, especially HBV, and underscores the importance of monitoring these high-risk groups. CONCLUSION In conclusion, HBV-related cirrhosis strongly correlates with HCC, with male sex, older age, viral hepatitis, elevated blood ammonia, and lower albumin and platelet levels increasing the risk of HCC.

Insights and future directions in studying intestinal microbiota post-transjugular intrahepatic portosystemic shunt for hepatitis B virus-related portal hypertension

The gut microbiota (GM) plays a major role in the progression and treatment response of liver diseases, with diverse compositions based on different etiologies. In China, hepatitis B virus (HBV) infection is the leading cause of cirrhosis and affects the GM composition in patients with cirrhosis-related portal hypertension (PH). However, a few studies have been conducted on GM alterations after transjugular intrahepatic portosystemic shunt (TIPS) in patients with HBV-related PH. A recent study investigated the changes in the GM in these patients after TIPS. This study found an increase in potentially pathogenic bacteria and a decrease in beneficial bacteria post-TIPS, particularly in patients with hepatic encephalopathy (HE), indicating the potential role of the GM in HE prediction and management post-TIPS. Nevertheless, the study had several limitations, including a small sample size, limited follow-up, a single time point for sample collection, and inadequate analysis of the correlation between intestinal flora, HBV infection status, and clinical parameters. Future research should address these limitations by expanding the sample size, prolonging the follow-up duration, collecting samples at multiple time points, and conducting comprehensive analyses to confirm the findings and evaluate the effectiveness of individualized microbiome-based therapies.

Comparison of anti-SARS-CoV-2 activity of some commercial dairy products.

The continuing emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be ameliorated by infection prevention through daily diet. In this study, we examined the anti-SARS-CoV-2 activity of 10 commercially available dairy products. They did not show any cytotoxicity against VeroE6/transmembrane protease serine 2 (TMPRSS2) cells (CC50 > 4 mg/ml). Importantly, these cells were checked using the cytopathic effect (CPE) assay, and 4 mg/ml dairy products reduced virus-induced CPE by more than 30%. Notably, Icreo akachan milk, an infant formula, showed the highest antiviral activity with an IC50 of 1.4 mg/ml. We assessed the effects of the dairy products on the entry of SARS-CoV-2 pseudovirus. R1 and Yakult, lactic acid bacterial beverages, inhibited viral entry with IC50 of 2.9 and 3.5 mg/ml, respectively. Collectively, these results indicate that commercially available dairy products moderately inhibit SARS-CoV-2 infection and may reduce the incidence of viral infections.

Epstein-Barr virus infection upregulates extracellular OLFM4 to activate YAP signaling during gastric cancer progression

Extracellular vesicles (EVs) are known to mediate cell communications and shape tumor microenvironment. Compared to the well-studied small EVs, the function of large microvesicles (MVs) during tumorigenesis is poorly understood. Here we show the proteome of MVs in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC), and identify olfactomedin 4 (OLFM4) is induced by EBV infection and secreted via MVs to promote tumor progression through Hippo signaling. Specifically, OLFM4 is a target gene of the cGAS-STING pathway, and EBV infection activates cGAS-STING pathway and increases OLFM4 expression. Moreover, MV-carried OLFM4 binds with the extracellular cadherin domain of FAT1, thereby impairing its intracellular interaction with MST1 and leading to YAP activation in recipient cells. Together, our study not only reveals a regulatory mechanism though which viral infection is coupled via MVs with intercellular control of the Hippo signaling, but also highlights the OLFM4-Hippo axis as a therapeutic target for EBV-associated cancers.

Human adenovirus type 7 (HAdV-7) infection induces pulmonary vascular endothelial injury through the activation of endothelial autophagy

BackgroundHAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous studies have shown a significant increase in serum levels of vascular permeability factor (VPF/VEGF) and viral load in pediatric patients with fatal HAdV-7 infection, suggesting potential damage to the pulmonary vascular endothelium. Further research is necessary to elucidate the underlying mechanism.MethodsThe human lung microvascular endothelial cell line-5a and human CD46 mice were used for in vitro and in vivo experiments, respectively. RNA-seq was employed for correlative omics analysis. Viral infection and copy status were examined using transmission electron microscopy to observe virus particles, immunofluorescence to detect the viral protein Hexon, and qPCR to assess HAdV-7 fiber gene copies. Various methods, including ELISAs for VEGF and other injury markers, the CCK8 assay for cell viability, and flow cytometry for endothelium numbers, were employed to evaluate endothelial damage. Acute lung injury severity was evaluated by scoring pathological inflammation and measuring pulmonary vascular permeability. Autophagy activation was assessed by observing autophagosomes and validating marker proteins.ResultsGSEA analysis showed significant enrichment of gene sets related to endothelial functions (barrier, defense, and regeneration) and ALI in the HAdV-7-infected group. GO analysis indicated an enrichment of autophagy-related pathways linked to cell death. Subsequently, successful signs of HAdV-7 infection and replication were observed in the endothelium, including cytopathic effects, intracellular virions, and increased HAdV-7 fiber gene copies. Endothelial injury, including mitochondrial damage, decreased endothelium, and elevated levels of endothelial injury markers such as VEGF, sICAM-1, sVCAM-1, E-selectin, ESM1, MCP1, and IL1β were observed after HAdV-7 infection. Additionally, evidence of leaky lung blood vessels and ALI was observed, including progressive weight loss, elevated pulmonary vascular permeability, and severe lung consolidation. Furthermore, HAdV-7 infection induced autophagosome formation in the endothelium and triggered complete cell autophagy. Importantly, inhibiting autophagic flux reduced VEGF levels and other endothelial injury markers, decreased viral load, improved cell survival rate, alleviated pulmonary vessel leakage, and mitigated lung inflammation.ConclusionsHAdV-7 successfully infects pulmonary vascular endothelium and replicates effectively, causing injury to the endothelium, high VEGF expression and viral load in the serum, as well as ALI/ARDS. Autophagy inhibitors can alleviate endothelial injury, inhibit viral replication, relieve leakage from the vasculature, and reduce lung inflammation.

A viral protein activates the MAPK pathway to promote viral infection by downregulating callose deposition in plants

Mitogen-activated protein kinase (MAPK) cascades are evolutionarily conserved in both plants and animals and play critical roles in activating innate immunity to defend against various pathogens. However, the role of MAPK cascades in positively regulating or enhancing viral infections in plants is unclear. In this study, we investigate the involvement of MAPK cascades in infection by the positive-strand RNA virus tomato chlorosis virus (ToCV). Our findings reveal that ToCV infection activates MAPK cascades, promoting virus spread within plants. Specifically, ToCV P7, a pathogenicity determinant protein, localizes to the plasma membrane and recruits NbMPK3/6 from the nucleus. Subsequently, P7 is directly phosphorylated on serine 59 by NbMPK3/6. Phosphorylated P7 interacts with NbREM1.1 and inhibits its ability to induce callose deposition at plasmodesmata. These results demonstrate that NbMPK3/6 directly phosphorylate ToCV P7, modulating antiviral defence mechanisms by downregulating callose deposition at plasmodesmata and thereby enhancing ToCV transmission in N. benthamiana. This study sheds light on the intricate arms race between host defence and viral counter-defence strategies.

Repurposing Drugs for Infectious Diseases by Graph Convolutional Network with Sensitivity-Based Graph Reduction.

Computational systems biology employs computational algorithms and integrates diverse data sources, such as gene expression profiles, molecular interactions, and network modeling, to identify promising drug candidates through repurposing existing compounds in response to urgent healthcare needs. This study tackles the urgent need for rapid therapeutic development against emerging infectious diseases. We introduce a novel analytic expression for sensitivity analysis based on the Kronecker product and enhance model prediction performance using Graph Convolutional Networks (GCNs) with sensitivity-based graph reduction. Our algorithm refines prediction performance by leveraging sensitivity-based graph reduction. By integrating RNA-seq data, molecular interactions, and GCNs, we identify disease-related genes and pathways, construct heterogeneous graph models, and predict potential drugs. This approach involves novel analytical expressions that assess sensitivity to model loss, employing the Kronecker product approach. Subgraph analysis identifies nodes for removal, leading to a refined graph used for model retraining. This cost-effective pipeline focuses on computational methods for drug repurposing, targeting infectious diseases such as Zika virus and COVID-19 infection. Applied to these infections, our methodology integrates 659 proteins and 703 drugs for Zika virus, and 495 proteins and 468 drugs for COVID-19, along with their interactions derived from gene expression profiles. Top candidate drugs, such as Betamethasone phosphate and Bizelesin for Zika virus, and Chloroquine, Heparin Disaccharide, and Resveratrol for COVID-19, were validated through literature review or docking analysis. This scalable approach demonstrates promise in repurposing drugs for urgent healthcare challenges.

Functional B cell deficiency promotes intrahepatic HBV replication and impairs the development of anti-HBV T cell responses.

The pivotal role of antibody-producing B cells in controlling hepatitis B virus (HBV) infection is well-established. However, the antiviral role of B cells extends beyond antibody production, which has been insufficiently studied for HBV infection. Using an HBV hydrodynamic injection (HDI) mouse model with B cell depletion or functional blockade, we detected HBV infection markers and assessed T cell function through enzyme-linked immunosorbent assay, RT-PCR and flow cytometry. We observed significantly delayed serum and intrahepatic HBV clearance in permanently B cell-deficient and transiently B cell-depleted mice as well as mice with a functional B cell blockade. Blocking B cell function prior to or soon after HBV HDI resulted in delayed HBV clearance indicating that B cells contribute to initiating anti-HBV immune responses after following HBV exposure. Additionally, we also found an early activation of B cells following HBV exposure, characterized by an upregulation of MHC-II, CXCR5, and PD-1. Critically, the proliferation and activation of both CD4 + and CD8 + T cells were impaired after B cell depletion prior to HBV challenge. Consistently, depleting B cells reduced the generation of Th1, Th2, and Th17 cells in the spleen and hindered HBV-specific CD8 + T cell responses in the liver. Along these lines, the HBV-exposed B cells were more efficient in inducing HBcAg-specific CD8 + T cell responses in vitro. Collectively, our data indicate that B cells, in addition to antibody production, are essential for the development of anti-HBV cellular responses and intrahepatic HBV clearance during the early stage of HBV antigen exposure.

Survival difference in patients treated with extracorporeal membrane oxygenation in COVID-19 vs. non-COVID ARDS: a systematic review and meta-analysis.

The COVID-19 pandemic has emphasized the need for effective management of severe acute respiratory distress syndrome (ARDS) using veno-venous extracorporeal membrane oxygenation (VV-ECMO). This meta-analysis aims to compare the effectiveness and outcomes of ECMO in patients with COVID-19 ARDS versus those with non-COVID ARDS, assessing its role in different respiratory virus infections. A systematic search was conducted in PubMed, Web of Science, and other relevant databases up to June 30, 2023, to identify studies comparing ECMO use in COVID-19 and non-COVID ARDS cases. This analysis adheres to PRISMA guidelines, with studies rigorously selected based on predefined inclusion and exclusion criteria and assessed for bias using validated tools. The meta-analysis included 24 studies with 2,121 patients, revealing that non-COVID ARDS patients treated with ECMO had a lower mortality risk compared to those with COVID-19 ARDS. Specifically, the overall pooled risk difference in survival was -0.11 (95% CI: -0.17 to -0.05, P<0.001), indicating a statistically significant advantage for non-COVID patients. The standardized mean difference for ECMO duration was significantly longer in COVID-19 patients (SMD=0.70, 95% CI: 0.32 to 1.08, P<0.001), reflecting more prolonged treatment needs. ECMO serves as a vital intervention in severe ARDS, with differential effectiveness observed between COVID-19 and non-COVID patients. The study's findings underline the need for precise patient selection and tailored ECMO application across different viral etiologies. These insights are crucial for enhancing clinical strategies and resource allocation during ongoing and future pandemics.

Swine IFN cocktail can reduce mortality and lessen the tissue injury caused by African swine-fever-virus-infected piglets

African swine fever (ASF), a highly virulent viral infection, poses a significant threat to the global pig industry. Currently, there are no commercially available vaccines against ASF. While the crucial role of interferon (IFN) in combating viral infections is well-established, its impact on the clinical signs and mortality rates of ASF remains unclear. In this study, swine IFN-α2, IFN-γ, and IFN-λ3 were fused with the Fc segment of immunoglobulin G (IgG) and expressed in mammalian cells (293T), and the antiviral efficacy were detected by VSV-3D4/2 and VSV-PK15 systems. Then, the interferon stimulating genes (ISGs) induced by IFNs-hFc in 3D4/2 cells were determined by qRT-PCR. Also, the preventive potential of the interferon (IFN) cocktail (a mixture of IFNα2-hFc, IFNγ-hFc, and IFNλ3-hFc) were evaluated in vivo by 25-day-old piglets. The results showed that the specific activities of IFNα2-hFc, IFNγ-hFc, and IFNλ3-hFc were 2.46 × 107 IU/mL, 4.54 × 109 IU/mL and 7.54 × 1010 IU/mL, respectively. The IFN-hFc significantly induced the expression of various IFN-stimulated genes (ISGs) in 3D4/2 cells after IFNs-Fc treatment, including IFIT5, Mx1, OASL, ISG12, STAT1, IRF1, PKR, CXCL10, and GBP1. Furthermore, the IFN cocktail treatment reduced the viral load, delayed death, and reduced tissue injury in the piglets infected with ASF virus (ASFV). in conclusion, these results suggest that the IFNs-hFc showed high anti-viral activity, and the IFN cocktail may be potential for the prevention and treatment of ASF.

Epstein-Barr virus and immunity.

The Epstein-Barr virus has infected the vast majority of the world's population. EBV is the most common herpes virus in the human population. In childhood, viral infection is either asymptomatic or can lead to infectious mononucleosis. In a small proportion of latently infected people, especially in immunosuppressed patients, EBV causes lymphoid and epithelial malignancies and a number of autoimmune diseases, including one of the causes of the development of multiple sclerosis. Innate immunity is the first line of antiviral defense, which EBV evades using a number of strategies to achieve successful infection. EBV disrupts the innate immune signaling pathways activated by Toll-like, RIG-I-like, NOD-like and AIM2-like receptors, as well as cyclic GMP-AMP synthetase. EBV also antagonizes interferon production and signaling, including the TBK1-IRF3 and JAK-STAT pathways. Through differential modulation of proviral and antiviral mechanisms of action of caspases and other cellular life cycle regulators at different stages of infection, EBV actively interferes with apoptotic and inflammatory pathways to continue effective infection. By turning the activation of innate immunity to its advantage by triggering a pro-inflammatory reaction and proteolytic cleavage of caspases that exhibit proviral activity, the virus establishes latency or enters the lytic reactivation phase, which contributes to the development of serious life-threatening diseases, including oncogenesis. The outcome of EBV infection is regulated by a subtle interaction between innate, adaptive immunity, and viral replication. In the absence of licensed preventive vaccines, immunocorrection and antiviral therapy are the only possible ways to combat the virus and prevent diseases associated with it. Understanding the mechanisms of action of certain EBV genes involved in the life cycle at different stages of infection will help in the future to find the right approach to the development of preventive and therapeutic drugs against EBV.

Discovery of New 1,2,4-Triazole/1,3,4-Oxadiazole-Decorated Quinolinones as Agrochemical Alternatives for Controlling Viral Infection by Inhibiting the Viral Replication and Self-Assembly Process.

Tobacco mosaic virus (TMV), a representative plant virus, is widely known and causes severe crop losses worldwide. In order to ensure the demand for crop and food security, the exploration of novel antiviral agents with outstanding activity and unique mechanisms of action is necessary. Herein, 40 new azole-quinolinone molecules were elaborately designed and systematically evaluated for their anti-TMV activity. Notably, compound A21 had significant therapeutic activity against TMV (EC50 value = 200 μg/mL), which was superior to commercial ningnanmycin (280 μg/mL). Studies on the anti-TMV mechanism showed that compound A21 could suppress the expression level of important TMV genes and affect the assembly of TMV viral particles by disrupting the self-assembly process of TMV coat protein (TMV-CP). In-depth antiviral behaviors were verified by molecular docking, fluorescence titration analysis, and TMV assembly assays, suggesting that compound A21 strongly interacted with TMV coat protein through various interactions. Overall, this promising work discloses a new paradigm for the exploitation of 2-quinolinone-based virucidal agents for hindering plant viral infection through triggering versatile antiviral behavior.

Investigating the Impact of Host Factors on Vaccinia Virus Infection Through Single-Cell Analysis via Flow Cytometry.

To investigate the impact of a host factor on viral replication, conventional techniques involve analyzing viral replication within a homogeneous cell population engineered to uniformly express the host factor. In this chapter, we present a method to explore the intricate dynamics between host factors and vaccinia virus (VACV) infection using flow cytometry, which enables the rapid, multi-parametric analysis of individual cells in solution. Cultured cells are transfected to express a host factor fused with a fluorescent protein, followed by infection with a VACV encoding a different fluorescent reporter. Subsequently, cells are washed, fixed, and filtered for flow cytometry analysis. The data are then analyzed with flow cytometry analysis software to evaluate the influence of the host factor on various infection parameters, including the stage of viral infection and viral replication level. This method allows for the precise investigation of proviral or antiviral factor expression in relation to viral replication within a heterogeneous population of cells.

Dynamics analysis of epidemic spreading with individual heterogeneous infection thresholds

In the real world, individuals may become infected with an epidemic after multiple exposures to the corresponding virus. This occurs because each individual possesses certain physical defenses and immune capabilities at the time of exposure to the virus. Repeated exposure to the virus can lead to a decline in immune competence, consequently resulting in epidemic infection. The susceptibility of individuals to an epidemic is heterogeneous. We model this characteristic as the individual heterogeneous infection threshold. Then, we propose an individual logarithmic-like infection threshold function on a single-layer complex network to reflect the heterogeneity of individual susceptibility on infecting the virus and the associated epidemic. Next, we introduce a partition theory based on the edge and logarithmic-like infection threshold function to qualitatively analyze the mechanisms of virus infection and epidemic spreading. Finally, simulation results on Erdő–Rényi (ER) and scale-free (SF) networks indicate that increasing both the epidemic infection initial threshold and outbreak threshold, as well as decreasing the virus and epidemic infection probability, can all effectively suppress epidemic spreading and epidemic infection outbreak. With an increase in the epidemic infection outbreak threshold, the increasing pattern of the final epidemic infection scale transitions from a second-order continuous phase transition to a first-order discontinuous phase transition. Additionally, degree distribution heterogeneity also significantly impacts the outbreak and spread of diseases. These findings provide valuable guidance for the formulation of immunization strategies.

Zelsuvmi: a promising treatment for molluscum contagiosum

Molluscum contagiosum (MC) is a common skin infection caused by a poxvirus, primarily affecting children and immunocompromised adults. It manifests as single or multiple raised, pearl-like papules and is highly contagious, spreading through skin contact or contaminated objects. Traditional treatments include cryosurgery, curettage, and pulsed dye laser ablation. However, in early 2024, berdazimer topical gel, 10.3% (ZELSUVMITM), was approved as the first topical treatment for MC. This review explores the potential of Zelsuvmi gel as a significant advancement in treatment due to its nitric oxide (NO)-producing properties. NO is a naturally occurring molecule in the body with multiple roles, including immune defense, antimicrobial activity, and modulation of apoptosis, inflammation, and cytokine production. The novel mechanism of action of Zelsuvmi, utilizing NO’s antiviral properties, has demonstrated compelling efficacy in clinical settings. The article also considers the broader implications of this treatment, not only for current dermatological practice but also for future research into innovative therapies for viral skin infections. Through an evaluation of clinical data, this review highlights Zelsuvmi’s potential to transform treatment approaches for MC, offering a non-invasive, effective option that may influence both clinical management and future prevention strategies.

Extracellular vesicles and micro-RNAs in liver disease.

Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in recipient cells for upregulating or downregulating a specific pathway. Injured hepatocytes secrete EV-associated miRNAs which can be taken up by liver sinusoidal endothelial cells (LSECs), immune cells, hepatic stellate cells (HSCs), and other cell types. In addition, these recipient cells will secrete their own EV-associated miRNAs to propagate a response throughout the tissue and the circulation. In this review, we comment on the implications of EV-miRNAs in the progression of alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), viral and parasitic infections, liver fibrosis, and liver malignancies. We summarize how circulating miRNAs can be used as biomarkers and the potential of utilizing EVs and miRNAs as therapeutic methods to treat liver disease.

Epidemiology of viral respiratory infections in pre- and during Covid-19 pandemic in “R. Dulbecco” University Hospital of Southern Italy

Not available.

Augmenting Adherence: Improving Medication Compliance and Patient Education in Anti-Retroviral Therapy through Graphical Representation.

Anti-Retroviral Therapy (ART) is a fundamental principle in the management of Human immunodeficiency virus (HIV) infection, significantly improving the quality of life for individuals living with the virus. However, the success of ART crucially depends on patient adherence to complex medication regimens that come with the therapy. Patients must meticulously adhere to their prescribed treatment plans to maintain viral suppression and prevent the progression of HIV. Medication adherence, a multifaceted challenge in healthcare, becomes particularly entangled within the realm of ART. Patients are often prescribed a combination of antiretroviral medications, each with unique dosing schedules and dietary requirements as instructed by the physician. For individuals with varying levels of health literacy, language proficiency, and cultural backgrounds, comprehending and adhering to these regimens can be overwhelming and challenging. Non-adherence to these medications can result in treatment failure, drug resistance, and compromised health outcomes that burden the healthcare systems. In that perspective, the role of pictograms as visual aids emerges as part and parcel of patient education and counseling within healthcare systems. Pictograms are graphical representations of concepts or actions designed to transcend linguistic and literacy barriers. When used in conjunction with ART, they simplify complex medication instructions, empower patients with knowledge, and improve adherence. Generally, the role of pictograms in supporting medication adherence and patient counseling in antiretroviral therapy is a powerful testament that serves a purpose in bridging communication and literacy gaps within the healthcare systems. By simplifying complex medication regimens, empowering patients with knowledge, and fostering adherence, pictograms contribute to better health outcomes and the overall success of ART. As healthcare providers and systems continue to harness the potential of pictograms, patient education and adherence in the management of HIV and other chronic conditions stand to be greatly enhanced.

ANTIVIRAL IL-33-STUMULATED GROUP 2 INNATE LYMPHOID CELLS (CD-90 AND CD-117) FROM MOUSE LUNGS

This article represents not only a significant scientific value, but also a great teaching and instruction value for researchers and motivated students to improve the skill spectrum in flow cytometry. This article provides step-by- step procedure description and results based on in vivo studies on murine lung tissue, cell of interest isolation with dual protocols for flow cytometry method as well as IL-33 impact in dynamics. The newly described innate lymphoid cells of group 2 (ILC2) play an important role in type 2 immune reactions, epithelial repair in mucosal tissue and metabolic homeostasis. ILC2 releases large amounts of type 2 cytokines such as interleukin 4 (IL-4), IL-5 and IL-13, which stimulate type 2 immunity, such as protection against worms. However, without strict regulation, the level of ILC2 can cause undesirable type 2 immune pathologies, including allergic inflammation of the respiratory tract, hypersensitivity of the respiratory tract and atopic dermatitis. Viral infections of the respiratory tract, which are typical triggers of type 1 immune reactions, often lead to type 2 pulmonary immune pathologies, such as asthma and its exacerbations. Interestingly, pulmonary virus infections induce the release of IL-33 with subsequent induction of ILC2-mediated type 2 pulmonary immunopathology, which is independent of the adaptive immune system.

Nonhuman primate models of pediatric viral diseases

Infectious diseases are the leading cause of death in infants and children under 5 years of age. In utero exposure to viruses can lead to spontaneous abortion, preterm birth, congenital abnormalities or other developmental defects, often resulting in lifelong health sequalae. The underlying biological mechanisms are difficult to study in humans due to ethical concerns and limited sample access. Nonhuman primates (NHP) are closely related to humans, and pregnancy and immune ontogeny in infants are very similar to humans. Therefore, NHP are a highly relevant model for understanding fetal and postnatal virus-host interactions and to define immune mechanisms associated with increased morbidity and mortality in infants. We will discuss NHP models of viruses causing congenital infections, respiratory diseases in early life, and HIV. Cytomegalovirus (CMV) remains the most common cause of congenital defects worldwide. Measles is a vaccine-preventable disease, yet measles cases are resurging. Zika is an example of an emerging arbovirus with devastating consequences for the developing fetus and the surviving infant. Among the respiratory viruses, we will discuss influenza and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We will finish with HIV as an example of a lifelong infection without a cure or vaccine. The review will highlight (i) the impact of viral infections on fetal and infant immune development, (ii) how differences in infant and adult immune responses to infection alter disease outcome, and emphasize the invaluable contribution of pediatric NHP infection models to the design of effective treatment and prevention strategies, including vaccines, for human infants.