Role of vitamin D in COVID-19 and other viral infections

Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources,primarily under the influence of UVB radiation.This essential nutrient has a vital role in numerous physiological processes,encom-passing immune function,cell growth,differentiation,insulin regulation,and cardiovascular well-being,along with its pivotal role in sustaining the delicate equilibrium of calcium and phosphate concentrations in the body.Moreover,vitamin D reinforces mucosal defense and bolsters the immune system through immunomodulation,making it a critical component of overall health.Numerous studies have unveiled the profound connection between vitamin D and the predisposition to respiratory tract infections,including well-known viruses such as influenza and the novel severe acute respiratory syndrome coronavirus 2.Vita-min D deficiency has been consistently linked to increased severity of coronavirus disease 2019(COVID-19)and a heightened risk of mortality among afflicted individuals.Retrospective observational studies have further substantiated these findings,indicating that levels of vitamin D are linked with both the occurrence and severity of COVID-19 cases.Vitamin D has its influence on viral infections th-rough a multitude of mechanisms,such as promoting the release of antimicrobial peptides and fine-tuning the responses of the immune system.Additionally,vitamin D is intertwined with the intricate network of the renin–angiotensin system,suggesting a potential impact on the development of complications related to COVID-19.While further clinical trials and extensive research are warranted,the existing body of evidence strongly hints at the possible use of vitamin D as a valuable tool in the prophylaxis and management of COVID-19 and other viral infectious diseases.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Monocyte and macrophage function in respiratory viral infections

Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.

Viral infections and cell cycle G2/M regulation

Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well- characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.

Viral infections in inflammatory bowel disease:Tips and tricks for correct management

Over the past decades,the treatment of inflammatory bowel diseases(IBD)has become more targeted,anticipating the use of immune-modifying therapies at an earlier stage.This top-down approach has been correlated with favorable short and long-term outcomes,but it has also brought with it concerns regarding potential infectious complications.This large IBD population treated with immunemodifying therapies,especially if combined,has an increased risk of severe infections,including opportunistic infections that are sustained by viral,bacterial,parasitic,and fungal agents.Viral infections have emerged as a focal safety concern in patients with IBD,representing a challenge for the clinician:they are often difficult to diagnose and are associated with significant morbidity and mortality.The first step is to improve effective preventive strategies,such as applying vaccination protocols,adopt adequate prophylaxis and educate patients about potential risk factors.Since viral infections in immunosuppressed patients may present atypical signs and symptoms,the challenges for the gastroenterologist are to suspect,recognize and diagnose such complications.Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients’lives.This practical review supports this standard of care to improve knowledge in this subject area.

Renal cell carcinoma and viral infections:A dangerous relationship?

Virus-related cancers in humans are widely recognized,but in the case of renal cancer,the link with the world of viruses is not clearly established in humans,despite being known in animal biology.In the present review,we aimed to explore the literature on renal cell carcinoma(RCC)for a possible role of viruses in human RCC tumorigenesis and immune homeostasis,hypothesizing the contribution of viruses to the immunogenicity of this tumor.A scientific literature search was conducted using the PubMed,Web of Science,and Google Scholar databases with the keywords“virus”or“viruses”or“viral infection”matched with(“AND”)“renal cell carcinoma”or“kidney cancer”or“renal cancer”or“renal carcinoma”or“renal tumor”or“RCC”.The retrieved findings evidenced two main aspects testifying to the relationship between RCC and viruses:The presence of viruses within the tumor,especially in non-clear cell RCC cases,and RCC occurrence in cases with pre-existing chronic viral infections.Some retrieved translational and clinical data suggest the possible contribution of viruses,particularly Epstein-Barr virus,to the marked immunogenicity of sarcomatoid RCC.In addition,it was revealed the possible role of endogenous retrovirus reactivation in RCC oncogenesis,introducing new fascinating hypotheses about this tumor’s immunogenicity and likeliness of response to immune checkpoint inhibitors.

Stem cell-like memory T cells:Role in viral infections and autoimmunity

Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs.

Changes in Phyto-Chemical Status upon Viral Infections in Plant:A Critical Review

Most damaging plant diseases have been caused by viruses in the entire world.In tropical and subtropical areas,the damage caused by plant virus leads to great economic and agricultural losses.Single stranded DNA viruses(geminiviruses)are the most perilous pathogens which are responsible for major diseases in agronomic and horticultural crops.Significantly begomoviruses and mastreviruses are the biggest genus of plant infecting viruses,transmitted though Bemisia tabaci and members of Cicadellidae respectively.Plants possesses some naturally existing chemicals term as phyto-chemicals which perform important functions in the plant.Some antioxidant enzymes are used by plants for selfdefense upon foreign invasion of infection.This review explains the present perceptive of influence of viral infections on phyto-chemicals,oxidative enzymes and biochemical changes occurring in the plant.Viral infection mediated phytochemical changes in plants mainly includes:up and down regulation of photosynthetic pigment,increase in the concentration of phenolic compounds,elevation of starch content in the leaf and up&down regulation of anti-oxidative enzymes including(GPX)guaiacol peroxidase,(PPO)polyphenol oxidase,(APX)ascorbate peroxidase,(SOD)superoxide dismutase and(CTA)catalase.These changes lead to initiation of hypersensitive response,by thicken of the leaf lamina,lignification under the leaf surface,blocking to stomatal openings,systematic cell death,generation of reactive oxidative species(ROS),activation of pathogen mediated resistance pathways i.e.,production of salicylic acid and jasmonic acid.Collectively all the physiological changes in the plant due to viral infection supports the activation of defense mechanism of the plant to combat against viral infection by limiting virus in specific area,followed with the production of barriers for pathogen,accumulation of starch in the leaf and excess production of(ROS).These strategies used by the plant to prevent the spread of virus in whole plant and to minimize the risk of severe yield loss.

Viral infections in orthopedics: A systematic review and classification proposal

BACKGROUND Although the impact of microbial infections on orthopedic clinical outcomes is well recognized,the influence of viral infections on the musculoskeletal system might have been underestimated.AIM To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme.METHODS We searched MEDLINE,Cochrane Central Register of Controlled Trials(CENTRAL),the Reference Citation Analysis(RCA),and Scopus for completed studies published before January 30,2021,to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries.Quality assessment was performed using SYRCLE's risk of bias tool for animal studies,Moga score for case series,Wylde score for registry studies,and Newcastle-Ottawa Scale for case-control studies.RESULTS Six human and four animal studies were eligible for inclusion in the qualitative synthesis.Hepatitis C virus was implicated in several peri-and post-operative complications in patients without cirrhosis after major orthopedic surgery.Herpes virus may affect the integrity of lumbar discs,whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss.CONCLUSION Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis.Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms.Therefore,based on our literature search,the proposed clinical and pathogenetic classification scheme is as follows:(1)Viral infections of bone or joint;(2)Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues;and(3)Viral infection as a risk factor for post-surgical bacterial infection.

The role of plasmacytoid dendritic cells(pDCs)in immunity during viral infections and beyond

Type I and III interferons(IFNs)are essential for antiviral immunity and act through two different but complimentary pathways.First,IFNs activate intracellular antimicrobial programs by triggering the upregulation of a broad repertoire of viral restriction factors.Second,IFNs activate innate and adaptive immunity.Dysregulation of IFN production can lead to severe immune system dysfunction.It is thus crucial to identify and characterize the cellular sources of IFNs,their effects,and their regulation to promote their beneficial effects and limit their detrimental effects,which can depend on the nature of the infected or diseased tissues,as we will discuss.Plasmacytoid dendritic cells(pDCs)can produce large amounts of all IFN subtypes during viral infection.pDCs are resistant to infection by many different viruses,thus inhibiting the immune evasion mechanisms of viruses that target IFN production or their downstream responses.Therefore,pDCs are considered essential for the control of viral infections and the establishment of protective immunity.A thorough bibliographical survey showed that,in most viral infections,despite being major IFN producers,pDCs are actually dispensable for host resistance,which is achieved by multiple IFN sources depending on the tissue.Moreover,primary innate and adaptive antiviral immune responses are only transiently affected in the absence of pDCs.More surprisingly,pDCs and their IFNs can be detrimental in some viral infections or autoimmune diseases.This makes the conservation of pDCs during vertebrate evolution an enigma and thus raises outstanding questions about their role not only in viral infections but also in other diseases and under physiological conditions.

Protein-based biomaterials for combating viral infections:Current status and future prospects for development

The outbreak of viral infections are serious threat to human life and health.However,there remains to be a lack of effective treatments and prophylactic measures against some viral infections.Additionally,there are numerous challenges in developing vaccines and antiviral drugs(e.g.,antibodies and protein inhibitors),such as low immunogenicity of vaccines,difficulties in storing vaccines,instability and easy degradation of protein drugs,and lack of drug selectivity.Protein-based biomaterials can interact with antiviral drugs or vaccines to achieve synergistic or enhanced effects,making them a promising antiviral tool with many advantages.Silk fibroin has the potential to stabilize liquid vaccines at room temperature.Elastin-like polypeptide modification can improve the stability and yield of virus-neutralizing antibodies.Drugs in combination withβ-casein or serum albumin(SA)has good prospects in treating human immunodeficiency virus(HIV)infections.Moreover,the greatest value of SA as a protein-based antiviral material lies in its ability to target the liver and macrophages.In the future,combination with SA(direct conjugation or encapsulation with drugs)may be a better treatment strategy for viral hepatitis and HIV infections because it leads to fewer adverse reactions.In addition,selfassembling protein nanoparticles(SApNPs)are found to improve vaccine immunogenicity.The combination of multiple viral immunogens and multiple SApNPs produces different promising vaccine candidates,thus highlighting the value of SApNPs.This review aimed to discuss the current status and future prospects for the development of protein-based biomaterials to combat viral infections.

Importance of etiologies of secondary diabetes:How often do we think off in clinical practice?

The article"Secondary diabetes due to different etiologies:Four case reports"by Song et al,published in the World Journal of Clinical Cases,delves into the identi-fication of rare causes of secondary diabetes and emphasizes the necessity for healthcare professionals to recognize these conditions.Failure to do so can result in treatment delays and compromised patient outcomes.The article discusses spe-cific types of diabetes,including maturity onset of diabetes in young,pancreas-related diseases,endocrinopathies,drug-induced diabetes,infections,and con-genital genetic syndromes associated with diabetes mellitus.Case summaries highlight how patients with secondary diabetes,stemming from conditions such as Williams-Beuren syndrome and pituitary adenoma,often exhibit distinct characteristics overlooked in clinical practice.The authors stress the importance of a holistic diagnostic approach and advocate for proactive management through early intervention,including genetic tests and antibody detection.Increased awa-reness and education are crucial for timely identification and proper management,ultimately improving patient well-being.These findings prompt a call to action for healthcare professionals to consider rare causes of secondary diabetes,facili-tating better glycemic control and overall patient care.

Effects of viral infection and microbial diversity on patients with sepsis:A retrospective study based on metagenomic next-generation sequencing

BACKGROUND: The study aims to investigate the performance of a metagenomic next-generationsequencing (NGS)-based diagnostic technique for the identifi cation of potential bacterial and viral infectionsand eff ects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients.METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for bloodcultures and metagenomic NGS when the patients’ body temperature was higher than 38 °C. Patients’demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded.The correlations between pathogen types and sepsis severity and survival rate were evaluated.RESULTS: NGS produced higher positive results (105 of 118;88.98%) than blood cultures(18 of 118;15.25%) over the whole study period. Concomitant viral infection correlated closelywith sepsis severity and had the negative effect on the survival of patients with sepsis. However,correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis.CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and thesurvival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviraldrugs combined with antibiotics may be benefi cial to ICU sepsis patients.

Fertility Care Provided by a Public Health Hospital to Viral-Infected Couples: A Case-Control Study

Objective: To evaluate the results of ART (clinical pregnancies and baby home rates) in couples infected with HBV, HCV, HIV or mixed in a Referral center. Patients: The study is a retrospective case-control study comprising 1587 cycles/1064 couples in the control group and 237 cycles/164 couples in the infected group, submitted to in vitro fertilization, intracytoplasmic sperm injection and embryo transfer. Two branches from the infected group were created: the HIV subgroup, comprising couples with one or both partners infected with HIV-1 (84 cycles/67 couples), and the HCV subgroup, including at least one partner infected with HCV (45 cycles/29 couples). Results: The infected group presented higher infertility duration (P < 0.001) and so did the HCV subgroup (P < 0.001). Tubal infertility was increased in the infected group (P < 0.001), and in the HIV (P < 0.001) and HCV (P = 0.01) subgroups. Oocytes and oocytes in metaphase II numbers were lower in the infected group, but not in the HIV and HCV subgroups. Clinical pregnancy rate was lower in the infected group (25.74%) when compared to the control (34.66%), probably due to the contribution of HCV individuals (17.78%), but not of HIV (28.57%). Baby home rate was lower in the infected group (21.52%) relative to the control group (28.42%), but no differences were found in the HIV (27.38%) and HCV (15.56%) subgroups. Conclusions: Despite the low clinical pregnancy rate in the HCV subgroup, baby home rates did not change from control. These data seem promising for couples with viral infections who wish to conceive.

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis,cancer,and liver failure.Liver cancer is the third leading cause of cancer-associated mortality,of which hepatocellular carcinoma(HCC)represents 90%of all primary liver cancers.Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management.Chronic infection with hepatitis B virus(HBV),hepatitis delta virus(HDV),and hepatitis C virus(HCV)are the greatest etiological risk factors for HCC.Due to the significant role of chronic viral infection in HCC development,it is important to investigate direct(viral associated)and indirect(immune-associated)mechanisms involved in the pathogenesis of HCC.Common mechanisms used by HBV,HCV,and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response,immune and viral protein-mediated oxidative stress,and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection,and metabolic reprogramming leading to steatosis is driven by HCV infection.The current review aims to provide a brief overview of HBV,HCV and HDV molecular biology,and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC,and current as well as emerging treatments for HCC.

RNA interference and antiviral therapy

RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms, strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.

RNAi,a new therapeutic strategy against viral infection

RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells.RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently,small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.

New animal models for hepatitis C viral infection and pathogenesis studies

Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection, including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.

Memory CD8+ T cell differentiation in viral infection: A cell for all seasons

Chronic viral infections such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are major global health problems affecting more than 500 million people worldwide. Virus-specific CD8+ T cells play an important role in the course and outcome of these viral infections and it is hypothesized that altered or impaired differentiation of virus- specific CD8+ T cells contributes to the development of persistence and/or disease progression. A deeper understanding of the mechanisms responsible for functional differentiation of CD8+ T cells is essential for the generation of successful therapies aiming to strengthen the adaptive component of the immune system.

Viral exploitation of actin: force-generation and scaffolding functions in viral infection

As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efficacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Specifically, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surfing, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.