Viral Inflammation Research Articles

Notch3 deletion regulates HIV-1 gene expression and systemic inflammation to ameliorate chronic kidney disease.

Antiretroviral therapy (ART) has decreased HIV-1 associated morbidity. However, despite ART, immune cells remain latently infected leading to chronic inflammation and HIV-1 associated comorbidities. New strategies are needed to target viral proteins and inflammation. We found activation of Notch3 in renal cells of the HIV-1 mouse model (HIV-Tg26) and in patients with HIV associated nephropathy. We hypothesized that targeting Notch3 activation constitutes an effective therapy for HIV-related chronic kidney diseases (HIV-CKD). We generated HIV-Tg26 mice with Notch3 knocked out (Tg-N3KO). Compared to HIV-Tg26 mice at 3 months, HIV-Tg-N3KO mice showed a marked reduction in renal injury, skin lesions and mortality rate. N3KO reduced renal infiltrating cells and significantly reduced the expression of HIV genes. Moreover, Notch3 activated the HIV- promoter and induction of HIV-1 increased Notch3 activation indicating a feedback mechanism. Further, bone marrow derived macrophages (BMDMs) from HIV-Tg26 mice showed activation of Notch3 indicating systemic effects. Consistent with that, systemic levels of TNF and MCP-1 were reduced in Tg-N3KO mice. Thus, Notch3 inhibition/deletion has a dual therapeutic effect in HIV-CKD and may extend to other HIV-related pathologies.

Update on Medical Management of Acute Peripheral Facial Palsy

Acute facial nerve palsy, particularly Bell’s palsy, is a common neurological disorder with an annual incidence of 20-30 cases per 100,000 individuals. It is characterized by sudden or gradual facial muscle palsy and is caused by viral reactivation, inflammation, or ischemia of the facial nerve. Prognosis varies widely, depending on the severity of nerve damage and timeliness of the intervention. Steroid therapy remains the cornerstone of Bell’s palsy treatment because it reduces inflammation and facilitates recovery. Early administration, preferably within 72 hours of symptom onset, considerably improves outcomes. However, the efficacy of combination therapy remains controversial. Current guidelines recommend oral steroids as the primary treatment for Bell’s palsy and suggest the selective use of antiviral agents in severe cases or when viral involvement is strongly suspected. For severe facial palsy, such as Ramsay Hunt syndrome or varicella-zoster virus-induced cases, combination therapy may improve outcomes and reduce sequelae; however, high-quality evidence is limited. Steroid therapy is the main treatment of Bell’s palsy and antiviral therapy can be added in severe cases to improve prognosis. Additional research is required to develop standardized guidelines, concerning the use of antiviral therapies in conjunction with steroids.

Circulating chemokine levels and receptor polymorphisms have potential as biomarkers for fibrosis stages in patients with chronic hepatitis C infection.

Chemokines and their receptors, which regulate lymphoid organ development and immune cell trafficking, are integral to the mechanisms underlying viral control, hepatic inflammation, and liver damage in chronic hepatitis C (CHC) infection. This study explores the potential relationship between serum chemokine levels/polymorphisms and hepatitis C infection in affected individuals, with a particular focus on their utility as biomarkers across different stages of fibrosis. Serum levels of the chemokines CXCL11, CXCL12, and CXCL16 were measured in patients with mild/moderate and advanced fibrosis due to CHC, as well as in healthy controls, using the ELISA method. The CXCL12 rs1801157 and CXCL16 rs2277680 polymorphisms were analyzed in blood samples from patients and healthy controls through RT-qPCR. Serum levels of CXCL11, CXCL12, and CXCL16 were significantly elevated in patients with advanced fibrosis compared to healthy controls. Furthermore, CXCL11 levels were markedly higher in patients with advanced fibrosis than in those with mild/moderate fibrosis. The frequency of the CXCL12 rs1801157 AA genotype was significantly higher in the advanced fibrosis group compared to the healthy control group. Similarly, the CXCL16 rs2277680 GA genotype was significantly more prevalent in the advanced fibrosis group than in the mild/moderate fibrosis group. The current study highlights that, in addition to the potential association between chemokine levels/polymorphisms and an increased risk of disease complications and pathological progression in CHC infection, serum CXCL11 levels and the CXCL16 rs2277680 allel polymorphism may be important factors in determining the fibrosis stage of hepatitis C infection.

Deficient neutrophil responses early in influenza infection promote viral replication and pulmonary inflammation.

Neutrophils play key protective roles in influenza infections, yet excessive neutrophilic inflammation is a hallmark of acute lung injury during severe infections. Phenotypic heterogeneity is increasingly recognized in neutrophil populations; however, how functional variation in neutrophils between individuals determine the diverse outcomes of influenza remains unclear. To examine immunologic responses that may drive varying outcomes in influenza, we infected C57BL/6 (B6) and A/J mice with mouse-adapted influenza A virus A/PR/8/34 H1N1. A self-resolving dose in B6 mice was lethal in A/J mice, which had increased viral load throughout infection accompanied by prominent bronchoalveolar neutrophilia and pulmonary vascular leakage preceding mortality. Notably, the B6 mice heavily recruited neutrophils to lungs early in infection while A/J mice failed to do so. Neutrophils from A/J mice additionally displayed reduced neutrophil extracellular trap (NET) release and reactive oxygen species (ROS) generation compared to B6 mice early in infection, suggesting the failure to control virus in A/J mice was a product of deficient neutrophil response. To determine if variation in neutrophils between strains governed viral control and inflammation, we adoptively transferred bone marrow neutrophils from B6 or A/J donors to A/J recipients early in infection and found that the transfer of B6 neutrophils enhanced viral clearance and abrogated the dissemination of CXCL1 and IL-6. The transfer of A/J neutrophils, however, failed to achieve either. Furthermore, B6 neutrophils were capable of greater levels of viral killing in vitro than their A/J counterparts. These results suggest that a key moderator of inflammation in influenza infection is the control of virus by neutrophils early in infection. Thus, host-specific differences in both the recruitment of these cells as well as interindividual variation in neutrophil ability to support viral clearance may in part dictate differing susceptibility to respiratory viral infections.

Long-term cognitive impairment, psychological disorders, and functional limitations in COVID-19 survivors: A 2-year follow-up at a tertiary care hospital in Bengaluru

Abstract Introduction: Given the COVID-19 pandemic, a significant number of patients experience postacute/long COVID-19. Neurological manifestations, possibly stemming from direct viral effects or systemic inflammation, are increasingly recognized. The current study aimed to better understand the psychological, cognitive, and functional outcomes of COVID-19 survivors 2 years postdischarge. Materials and Methods: This analytical cross-sectional study included 98 COVID-19 survivors aged ≥18 years, referred to a post-COVID-19 clinic, and informed consent was procured. After administering a semi-structured interview constituting sociodemographic details, treatment profile, and validated assessment tools, subjects were categorized based on anxiety, depression, cognitive failure, and functional disability scores accordingly. Results: The median age of participants was 55 years, with 58.2% being male. The median hospital stay was 13 days, and 27.6% required intensive care unit care. Anxiety, depression, and functional disability were prevalent in 22.1%, 25.3%, and 60% of participants, respectively. The median scores of the domains of cognitive failure, i.e., forgetfulness, distractibility, and false triggering among the subjects were 6, 5, and 6, respectively, out of the highest possible score of 32. Depression and functional disability were more common in those over 45 years, with lower education, and unemployed (P < 0.01). Increased anxiety (P < 0.01) was seen associated with longer hospital stays. Patients aged above 45 years had significantly higher scores of depression, cognitive failure, and anxiety. Depression and cognitive issues were associated with lower education and unemployment which correlated positively with anxiety and forgetfulness. Conclusion: Due to the significant correlation of certain sociodemographic and treatment factors with depression, anxiety, and domains of cognitive failure, early identification and treatment of the same through specialized clinics are crucial.

Prior influenza virus infection alleviates an arbovirus encephalitis by reducing viral titer, inflammation, and cellular infiltrates in the central nervous system.

Influenza viruses are medically important human pathogens that caused epidemics and pandemics throughout history. Conversely, encephalitic arthropod-borne virus (arboviral) diseases affect both humans and domestic animals, creating massive public health issues. Influenza viruses circulate globally while arboviruses dominate tropical regions. Given both influenza virus and encephalitic arboviruses, such as alphaviruses, circulate in many regions globally, co-infections are likely to occur. In addition, arthropod-borne neurotropic infections are generally mild or asymptomatic, hence are likely to be unnoticed as a risk factor during influenza infection. However, the consequences of such co-infections are unclear. Our recent study showed that alphavirus infection preceding Influenza A virus (IAV) infection negatively impacted immune responses to the influenza virus in mice. Here, we aim to investigate the immune responses when the order of sequential infection with IAV and alphavirus are swapped. Altogether, our findings will provide key insights to improved diagnostics, preventative vaccines, and antiviral therapies.

HBV‐Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment

ABSTRACTBackgroundChronic hepatitis B virus (HBV) infection is a common but underdiagnosed and undertreated health condition and is the leading cause of hepatocellular carcinoma (HCC) worldwide. HBV (rated a Grade 1 carcinogen by the International Agency for Research on Cancer) drives the transformation of hepatocytes in multiple ways by inducing viral DNA integrations, genetic dysregulation, chromosomal translocations, chronic inflammation, and oncogenic pathways facilitated by some HBV proteins. Importantly, these mechanisms are active throughout all phases of HBV infection. Nevertheless, most clinical guidelines for antiviral therapy recommend treatment based on a complex combination of HBV DNA levels, transaminasemia, liver histology, and demographic factors, rather than prompt treatment for all people with infection.AimsTo determine if current frameworks for antiviral treatment address the impacts of chronic HBV infection particularly preventing cancer development.Materials and MethodsWe reviewed the recent data demonstrating pro‐oncogenic factors acting throughout a chronic HBV infection can be inhibited by antiviral therapy.ResultsWe extensively reviewed Hepatitis B virology data and correlating clinical outcome data. From thi, we suggest that new findings support simplifying and expanding treatment initiation to reduce the incidence ofnew infections, progressive liver disease, and risk of hepatocellular carcinoma. We also consider lessons learned from other blood‐borne pathogens, including the benefits of antiviral treatment in preventing transmission, reducing stigma, and reframing treatment as cancer prevention.ConclusionIncorporating these practice changes into treatment is likely to reduce the overall burden of chronic HBV infections and HCC. Through this, we may better achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat and minimise its impact on people's lives.

Diagnostic challenges of diffuse leptomeningeal glioneuronal tumor in an adult female: illustrative case

BACKGROUND Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare central nervous system tumor, especially in adult females. Typically, it presents with leptomeningeal enhancements in the basal cisterns and spinal cord. However, varied radiological and pathological features can complicate the diagnosis, as the present case illustrates. OBSERVATIONS An adult female presented with severe headache, blurred vision, and cognitive impairment. Elevated intracranial pressure (ICP) was detected via lumbar puncture. Brain magnetic resonance imaging (MRI) revealed atypical unilateral basal cistern enhancement, differing from the usual symmetrical DLGNT presentation. Despite high ICP, only mild ventricular enlargement was observed. Noncontrast spine MRI failed to demonstrate spinal leptomeningeal enhancement. A stereotactic biopsy of an occipital lesion was inconclusive. These atypical findings led to misdiagnoses of viral encephalitis or inflammation at two hospitals. Significant symptom relief occurred only after ventriculoperitoneal (VP) shunt surgery. Over 2.5 years, intraparenchymal lesions in the parahippocampal gyrus grew, necessitating surgical intervention. Pathological examination finally confirmed DLGNT. Postsurgery, the patient underwent chemotherapy with temozolomide and remains symptom free. LESSONS This case underscores the critical importance of comprehensive initial imaging, strategic biopsy planning, and timely placement of a VP shunt in patients with DLGNT. It contributes to the literature by revealing atypical imaging features and long-term progression patterns of DLGNT. https://thejns.org/doi/10.3171/CASE24701

It's all in the gut: the central role of the gut and microbiome in preventing disease progression in simian immunodeficiency viruses infected African nonhuman primates.

Typically, both HIV-infected humans and simian immunodeficiency virus (SIV)-infected Asian nonhuman primates (NHPs) eventually progress to AIDS, while African NHPs that are natural hosts of SIV do not, in spite of life-long, high levels of viral replication. Lack of disease progression in African NHPs is not due to some adaptation by the virus, but rather to host adaptations to the virus. Central to these adaptations is maintenance of the gut integrity during acute viral replication and inflammation, which allows natural hosts to avoid the chronic inflammation characteristic to pathogenic HIV/SIV infection. It has been recently shown that natural hosts of SIVs, such as the African green monkey (AGM), avoid damage to the mucosal epithelium through wound healing mechanisms, possibly with the contribution of a unique anti-inflammatory microbiome. Furthermore, these mechanisms are independent of viral replication, and CD4+ T-cell activation or depletion. Future SIV research on natural hosts should focus on further elucidating the anti-inflammatory state of their gut, and the role of microbiome/dysbiosis in the pathogenesis of SIV infection, with the goal of development new regiments or treatments to reduce or even halt the vicious cycle of gut damage and inflammation triggered by pathogenic HIV/SIV infection.

Fatal Lassa fever in cynomolgus monkeys is associated with systemic viral dissemination and inflammation.

The pathogenesis of Lassa fever has not yet been fully deciphered, particularly as concerns the mechanisms determining whether acute infection is controlled or leads to catastrophic illness and death. Using a cynomolgus monkey model of Lassa virus (LASV) infection reproducing the different outcomes of the disease, we performed histological and transcriptomic studies to investigate the dynamics of LASV infection and the immune mechanisms associated with survival or death. Lymphoid organs are an early major reservoir for replicating virus during Lassa fever, with LASV entering through the cortical sinus of draining lymph nodes regardless of disease outcome. However, subsequent viral tropism varies considerably with disease severity, with viral dissemination limited almost entirely to lymphoid organs and immune cells during nonfatal Lassa fever. By contrast, the systemic dissemination of LASV to all organs and diverse cell types, leading to infiltrations with macrophages and neutrophils and an excessive inflammatory response, is associated with a fatal outcome. These results provide new insight into early viral dynamics and the host response to LASV infection according to disease outcome.

Formulation and Evaluation of Ginger Gargle

Nowadays, Throat infections are the common diseases that cause discomfort Ness, inconvenience and irritation. This project explores the potential therapeutic benefits of ginger gargle to soothe the throat infection. Ginger, known for its antimicrobial and effective tooth decay has been used from traditions for centuries. In this project, we investigate the ginger-based gargle effectiveness and reliving symptoms to accelerate the recovery process related to throat infection. The formulations and proportion of ginger gargle is done by controlled experiments to assess efficacy. We aim to determine the potential of ginger and apple cider vinegar as an antimicrobial and anti- inflammatory impact on the pain relief and overall well-being in individuals suffering from throat infection. Through preliminary test it suggests that the ginger contain phenol and terpenoids which may offer a promising natural remedy for throat infection which is potential to complement conventional treatment the outcome of the project shows potential benefit for those who’s seeking the complementary benefits over the conventional doses to manage the throat infection to enhance the quality of life. Gargle are liquid solution used for rinsing with warm water for 15-20 seconds in the mouth with your head tilted back to alleviate discomfort Ness or address specific throat and oral infection it provides soothing effect for condition like sore throat, mouth ulcer sinus infection, throat inflammation, viral respiratory inflammation, seasonal allergies. This project helps to research further into utilization of natural remedies like ginger in modern healthcare to access the solutions for common health issues through lesser side effects.

Viral intruders in the heart: A review of RNA viruses and their role in cardiac disorders.

Viral cardiac diseases have a significant impact on global health, and RNA viruses play a crucial role in their pathogenesis. This literature review aims to provide a comprehensive understanding of the complex relationship between RNA viruses and cardiac diseases, focusing on the molecular processes and clinical implications of these interactions. The paper begins by discussing the various RNA viruses that have been linked to cardiac infections. Subsequently, the study explores the mechanisms through which RNA viruses can cause cardiac injury, including direct viral invasion, immune-mediated responses, and molecular mimicry. The review extensively examines the intricate interplay between the host immune system and RNA viruses, shedding light on both protective and harmful immune responses. Additionally, it investigates the role of viral persistence and chronic inflammation in the long-term effects on cardiac health. The thorough analysis presented not only enhances our scientific understanding of how RNA viruses contribute to the development of cardiac diseases but also highlights potential avenues for future research and breakthroughs in this field. Given the significant global health threat posed by viral cardiac disorders, unraveling the molecular foundations of these diseases is essential for advancing diagnostic capabilities and therapeutic interventions.

Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides.

Extracellular vesicles (EVs) released by virus-infected cells have the potential to encapsulate viral peptides, a characteristic that could facilitate vaccine development. Furthermore, plasma-derived EVs may elucidate pathological changes occurring in distal tissues during viral infections. We hypothesized that molecular characterization of EVs isolated from COVID-19 patients would reveal peptides suitable for vaccine development. Blood samples were collected from three cohorts: severe COVID-19 patients (G1), mild/asymptomatic cases (G2), and SARS-CoV-2-negative healthcare workers (G3). Samples were obtained at two time points: during the initial phase of the pandemic in early 2020 (m0) and eight months later (m8). Clinical data analysis revealed elevated inflammatory markers in G1. Notably, non-vaccinated individuals in G1 exhibited increased levels of neutralizing antibodies at m8, suggesting prolonged exposure to viral antigens. Proteomic profiling of EVs was performed using three distinct methods: immunocapture (targeting CD9), ganglioside-capture (utilizing Siglec-1) and size-exclusion chromatography (SEC). Contrary to our hypothesis, this analysis failed to identify viral peptides. These findings were subsequently validated through Western blot analysis targeting the RBD of the SARS-CoV-2 Spike protein's and comparative studies using samples from experimentally infected Syrian hamsters. Furthermore, analysis of the EV cargo revealed a diverse molecular profile, including components involved in the regulation of viral replication, systemic inflammation, antigen presentation, and stress responses. These findings underscore the potential significance of EVs in the pathogenesis and progression of COVID-19.

Mediterranean Diet and Olive Oil Redox Interactions on Lactate Dehydrogenase Mediated by Gut Oscillibacter in Patients with Long-COVID-19 Syndrome.

Chronic viral inflammation is associated with oxidative stress and changes in gut microbiota. The Mediterranean diet (MD), with recognized anti-inflammatory and antioxidant properties, modulates gut microorganisms, specifically on the interaction between extra virgin olive oil, a key component of the MD with well-documented antioxidant effects. This study investigated the influence of adherence to MD and antioxidant-rich foods (extra virgin olive oil) on biochemical, inflammatory, and microbiota profiles in patients with chronic inflammation defined as a prolonged inflammatory response due to immune dysregulation following the acute phase of the viral infection. Participants were classified into low (n = 54) and high (n = 134) MD adherence groups (cut-off of 7 points based on previous studies utilizing the same threshold in the assessment of MD adherence). Gut microbiota was sequenced using the 16S technique, and the adherence to MD was assessed using a validated questionnaire for a Spanish population. High adherence to the MD was linked to significant improvements in inflammatory and oxidative stress markers, including reductions in LDL-cholesterol, glucose, and lactate dehydrogenase (LDH) levels, an indicative of redox balance, as well as a significant higher consumption of antioxidant foods. Moreover, gut microbiota analysis revealed distinct compositional shifts and a lower abundance of the Oscillibacter genus in the high adherence group. Notably, a significant interaction was observed between MD adherence and extra virgin olive oil consumption, with Oscillibacter abundance influencing LDH levels, suggesting that the MD antioxidant properties may modulate inflammation through gut microbiota-mediated mechanisms. These findings provide new evidence that adherence to the Mediterranean diet can reduce inflammatory markers in patients with long-COVID-19, a population that has not been extensively studied, while also highlighting the potential role of the bacterial genus Oscillibacter in modulating this effect.

Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?

Melatonin is a hormone naturally produced by the body that has recently been found to have antiviral properties. However, its antiviral mechanisms are not entirely understood. Using Caco-2 cells, we developed a gastrointestinal organoid model to investigate the impact of melatonin on cellular organoid culture response to Poly I:C-induced viral inflammation in the gastrointestinal tract. Melatonin was found to have different effect when applied as a pretreatment before the induction of viral inflammation or as a treatment after it. Melatonin pretreatment after Poly I:C stimulation did not protect organoids from size reduction but enhanced cell proliferation, especially when lower (1 and 10 µM) melatonin concentrations were used. On the other hand, treatment with melatonin after the induction of viral inflammation helped to maintain the size of the organoids while reducing cell proliferation. In pretreated cells, reduced IFNLR1 expression was found, while melatonin treatment increased IFNLR1 expression and reduced the production of viral cytokines, such as IFNλ1 and STAT1-3, but did not prevent from apoptosis. The findings of this study emphasize the importance of type III IFNs in antiviral defense in epithelial gastrointestinal cells and shed more light on the antiviral properties of melatonin as a potential therapeutic substance.

Exploration of common pathogenesis and candidate hub genes between HIV and monkeypox co-infection using bioinformatics and machine learning

This study explored the pathogenesis of human immunodeficiency virus (HIV) and monkeypox co-infection, identifying candidate hub genes and potential drugs using bioinformatics and machine learning. Datasets for HIV (GSE 37250) and monkeypox (GSE 24125) were obtained from the GEO database. Common differentially expressed genes (DEGs) in co-infection were identified by intersecting DEGs from monkeypox datasets with genes from key HIV modules screened using Weighted Gene Co-Expression Network Analysis (WGCNA). After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and construction of protein-protein interaction (PPI) network, candidate hub genes were further screened based on machine learning algorithms. Transcriptional factors (TFs) and miRNA-candidate hub gene networks were constructed to understand regulatory mechanisms and protein-drug interactions to identify potential therapeutic drugs. Seven candidate hub genes—MX2, ADAR, POLR2H, RPL5, IFI16, IFIT2, and RPS5—were identified. TFs and miRNAs associated with these hub genes, playing a key role in regulating viral infection and inflammation due to the activation of antiviral innate immunity, were also identified through network analysis. Potential therapeutic drugs were screened based on these hub genes: AZT, a nucleotide reverse transcriptase inhibitor, suppressed viral replication in HIV and monkeypox co-infection, while mefloquine inhibited inflammation due to the activation of antiviral innate immunity. In conclusion, the study identified candidate hub genes, their transcriptional regulation, signaling pathways, and small-molecule drugs in HIV and monkeypox co-infection, contributing to understanding the pathogenesis of HIV and monkeypox co-infection and informing precise therapeutic strategies.

Lithospermic acid inhibits dengue virus infection through binding with envelope proteins

The dengue virus has emerged as a global pandemic, highlighting the urgent need for the immediate development of antiviral therapeutics. Lithospermum erythrorhizon, a medicinal plant commonly used in China for various ailments including viral infections, inflammation, rheumatism, and cancer, showed promising antiviral properties in our research. Specifically, both the ethanol extract of Lithospermum erythrorhizon and its active component, lithospermic acid, demonstrated significant inhibitory effects on Dengue virus (DENV) replication in Vero cells, with EC50 values of 6.50 μg/mL(95 % CI: 2.25 to 18.98)and 15.00 μM(95 % CI: 12.13 to 18.07), respectively. Notably, lithospermic acid exhibited potent antiviral activity across multiple cell lines against DENV, impeding virus replication and specifically impeding the expression of viral E and NS3 proteins during the early stages of DENV infection. Experimental assays involving RNase digestion and sucrose density gradient analysis confirmed that lithospermic acid did not directly inactivate DENV but rather interfered with viral processes. Furthermore, the compound was found to bind to the E protein of DENV, effectively inhibiting viral infection and mitigating the cytopathic effects induced by DENV. Collectively, these findings underscore the potential of lithospermic acid as a promising candidate for the development of therapeutic strategies targeting DENV infection.

Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.

Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases. We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool. Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities. Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.

Single-cell spatiotemporal analysis of the lungs reveals Slamf9+ macrophages involved in viral clearance and inflammation resolution

How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9+ macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9+ macrophages contain SARS-CoV-2, recruit and interact with Isg12+Cst7+ neutrophils to clear the viruses. After viral clearance, Slamf9+ macrophages differentiate into Trem2+ and Fbp1+ macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9+ macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.

Rhesus rotavirus NSP1 mediates extra-intestinal infection and is a contributing factor for biliary obstruction.

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode non-structural protein 1 (NSP1) derived from different RV strains. We found that compared to the parental simian SA11 strain that is less biliary pathogenic, SA11 containing an RRV-derived NSP1 resulted in severe biliary obstructive disease comparable to that associated with RRV infection, reflected by high levels of viral RNA and inflammation in the biliary tract, liver, and pancreas. In contrast, RRV containing an SA11-originated NSP1 showed only mild biliary obstruction comparable to what was observed during SA11 infection. Infection with a monoreassortant RRV virus carrying NSP1 from the bovine RV UK strain also showed substantially reduced viral replication in extra-intestinal organs and did not develop clinical biliary diseases. Mechanistically, RRV NSP1 seemed to promote active viral replication in hepatocytes and this expanded tropism led to enhanced infiltration of CD4 and CD8 T cells, causing immunopathology and damage in the hepatobiliary system. These results highlight an unexpectedly important role of RV NSP1 in viral replication and disease progression in extra-intestinal tissues.