Reviews in Medical Virology最新文献

In the initial stage of the COVID-19 pandemic, high case fatality was noted. The case fatality during this was associated with the cytokine storm (CS) or cytokine storm syndrome (CSS). Sometimes, virus infections are due to the excessive secretion of pro-inflammatory cytokines, leading to cytokine storms, which might be directed to ARDS, multi-organ failure, and death. However, it was noted that several miRNAs are involved in regulating cytokines during SARS-CoV-2 and other viruses such as IFNs, ILs, GM-CSF, TNF, etc. The article spotlighted several miRNAs involved in regulating cytokines associated with the cytokine storm caused by SARS-CoV-2 and other viruses (influenza virus, MERS-CoV, SARS-CoV, dengue virus). Targeting those miRNAs might help in the discovery of novel therapeutics, considering CS or CSS associated with different virus infections.

SARS-CoV-2 is an oral pathogen that infects and replicates in mucosal and salivary epithelial cells, contributing to oral post-acute sequelae COVID-19 (PASC) and other oral and non-oral pathologies. While pre-existing inflammatory oral diseases provides a conducive environment for the virus, acute infection and persistence of SARS-CoV-2 can also results in oral microbiome dysbiosis that further worsens poor oral mucosal health. Indeed, oral PASC includes periodontal diseases, dysgeusia, xerostomia, pharyngitis, oral keratoses, and pulpitis suggesting significant bacterial contributions to SARS-CoV-2 and oral tissue tropism. Dysbiotic microbiome-induced inflammation can promote viral entry via angiotensin-converting enzyme receptor-2 (ACE2), serine transmembrane TMPRSS2 and possibly other non-canonical pathways. Additionally, metabolites derived from a dysbiotic microbiome can alter the physiological and biochemical pathways related to the metabolism of lipids, carbohydrates, and amino acids. This may promote a pro-inflammatory microenvironment, leading to immune exhaustion, loss of tolerance, and susceptibility to a variety of oral pathogens, causing acute and later chronic inflammation. Microbial release of mimics of host metallopeptidases related to furin, ADAM17 (A disintegrin and metalloproteinase 17), and glycoprotein metabolites can further aid viral attachment to T cell immunoglobulin-like (TIMs), enhancing viral entry while simultaneously depressing oral mucosal immune resistance and clearance. Membrane reorganization characterised by neuroproteins, such as neuropilins, also functionally assists with SARS-CoV-2 entry and extends the pathogenesis of PASC from the oral cavity to the brain, gut, or other non-oral tissues. Thus, poor oral health, characterised by disrupted oral microbiomes can promote viral tropism, weaken antiviral resistance, and heightens susceptibility to SARS-CoV-2 infection. This immune dysfunction also increases the risk of additional viral infections, exacerbating oral conditions like periodontal and endodontic diseases. These persistent oral health issues can contribute to systemic inflammation, creating bidirectional effects between oral and non-oral tissues, potentially leading to Post-Acute Sequelae of COVID-19 (PASC).

Arboviral infections in paediatric populations present unique challenges due to distinct pathophysiological mechanisms influenced by developmental and immunological differences. Commonly implicated arboviruses include dengue virus (DENV), Zika virus (ZIKV), chikungunya virus (CHIKV), West Nile virus (WNV), and yellow fever virus (YFV). These viruses exhibit specific tropisms, targeting organs such as the central nervous system (CNS), liver, and vasculature. Immune responses in children, characterised by an underdeveloped adaptive system and enhanced innate immunity, can exacerbate inflammation and increase susceptibility to severe outcomes such as dengue hemorrhagic fever (DHF), congenital Zika syndrome (CZS), and neuroinvasive complications. Maternal antibodies, antibody-dependent enhancement (ADE), and immature barriers, such as the blood-brain barrier, further contribute to disease severity. This review highlights the virological and immunological nuances of arboviral pathophysiology in paediatric patients, emphasising the need for age-specific diagnostic, therapeutic, and preventive strategies to mitigate the burden of these infections.

Zika virus (ZIKV) is a virus transmitted by arthropods that exhibits considerable pathogenicity, resulting in a significant health and economic impact worldwide. A rise in congenital anomalies has been noted in kids born to mothers who have infections during pregnancy, alongside a rise in neurological symptoms in adults. In this study, we reassessed the data on brain abnormalities in maternal infection with ZIKV during pregnancy through a systematic review and meta-analysis. A thorough search was carried out in the PubMed, Scopus, Web of Science and Embase databases to extract pertinent published data up to November, 2024. In this meta-analysis, 14 studies with 912 individuals were incorporated. Subgroup analyses, depending on the maternal age, gestational age at detection of brain abnormalities, the time of ZIKV diagnosis, type of sample and birth weight at delivery, were performed. Critical appraisal was completed using the Newcastle-Ottawa Scale (NOS) tools. In this analysis, we identified 14 studies that reported brain abnormalities in newborn infants with ZIKV-infected pregnant women, of which 58% studies were from Brazil. The overall birth defect with brain abnormalities was found to be (1.94 [95% CI: 1.3-2.7], P = 0.00). Of the most common brain abnormalities, microcephaly (OR: 2.7 [95% CI 1.5-4.7], P = 0.00), ventriculomegaly (OR: 1.7 [95% CI 0.91-3.3], P = 0.09) and corpus callosal anomaly (OR: 1.8 [95% CI 1.02-3.3], P = 0.04) had highest the risk in children with ZIKV-infected pregnant women. No publication bias was found when applying the Begg's rank correlation and Egger's linear regression tests (P = 1 and P = 0.44, respectively). subgroups of maternal age ≥ 30 years and gestational week of ZIKV diagnosis ≥ 25 weeks are important in zika-associated birth defects. This systematic review and meta-analysis evidenced a high risk of brain defects in ZIKV-infected pregnant women. Maternal age and gestational week of ZIKV diagnosis may modify this risk.

Human polyomaviruses (HPyVs) are a diverse group of viruses that typically establish asymptomatic persistent infections in healthy individuals. However, they can lead to severe diseases in immunocompromised patients. The past 15 years have witnessed significant advancements in understanding HPyVs, leading to the discovery of several novel and highly divergent strains. This surge in knowledge raises critical questions about their evolution, tropism, and potential contributions to various diseases. Although HPyVs are generally benign, certain strains can lead to significant health issues under immunocompromised conditions. Since 2007, several novel PyVs have been isolated from humans: Karolinska Institute Polyomavirus (KIPyV), Washington University Polyomavirus (WUPyV), Merkel cell Polyomavirus (MCPyV), HPyV6, HPyV7, Trichodisplasia spinulosa polyomavirus (TSPyV), HPyV9, HPyV10, Saint Louis polyomavirus (STLPyV), HPyV12, New Jersey Polyomavirus (NJPyV), Lyon IARC polyomavirus (LIPyV), HPyV16 and Quebec polyomavirus (QPyV). This review summarises the available data regarding the biology, tissue tropism, epidemiology, and associated diseases of novel HPyVs discovered from 2007 to the present. While some HPyVs are well-characterised with clear associations to specific diseases, others remain enigmatic, warranting additional investigation into their biology and clinical implications.

As Nipah virus (NiV) infection is characterised by a possible pandemic risk, being currently limited to a small but deadly belt, the attention of other countries is essential. It has often been pointed out that NiV is an under-researched virus with a high-risk potential. This study aimed to show the global research history and status quo based on analyses of various chronological and geographical parameters, including socioeconomic characteristics and research funding. For this purpose, advanced analysis methods and visualisation techniques were applied, such as density equalisation mapping and cluster analysis. The correlation between the number of articles on NiV and the economic strength or intensity of financing per country is significant. However, the comparatively low scientific commitment of countries that are usually among the major players in global scientific publications and the declining scientific interest in NiV research combined with the prevailing knowledge gaps in NiV infectiology in conjunction with the risk of NiV spreading to other areas is extremely threatening. Research on previous viruses such as Corona and mpox shows an equally short-term interest, which has led to an insufficiently prepared situation in the run-up to outbreaks, making it hard to find quick and effective solutions. As often said, the NiV infection belt is small but deadly, but global travel and trade increase the risk of spreading. The scientific community worldwide must be prepared for the possible spread of infections that pose a pandemic risk.

Alphaviruses are re-emerging vector-born pathogens that cause arthralgia or encephalitic diseases on a global scale. While a vaccine against chikungunya virus was recently approved, no vaccines currently exist for other alphaviruses, nor are there antiviral drugs for the treatment of alphavirus infections. Alphaviruses have positive-strand RNA genomes, and their RNA replication is coordinated by activities of the multifunctional nonstructural protein 2 (nsP2), a helicase-protease and a subunit of viral RNA replicase. We provide a comprehensive overview of nsP2 functions and inhibitors of its activities for their potential as effective antivirals. Furthermore, analysis of nsP2 activities suggests that it could be targeted to develop advanced live attenuated vaccines and strategies for controlling alphavirus transmission by mosquito vectors.

The signalling pathway of the nuclear factor of activated T cells (NFAT) plays a crucial role in regulating various cellular processes such as cardiac hypertrophy, adipose differentiation, chondrocyte development, angiogenesis, inflammation, immune system activation, organogenesis, cancer cell migration, differentiation and survival. In addition, the NFAT signalling pathway acts as a key regulator of viral infections. Accordingly, it is plausible to assume that viruses have developed different mechanisms to manipulate this pathway to promote their pathogenicity. Viral pathogens can either inhibit or upregulate NFAT signalling through various mechanisms, including modulation of calcineurin activity, calcineurin/NFAT interaction, NFAT stability and translocation, NFAT-DNA-binding activity and NFAT-transcription partner interaction. Therefore, the NFAT signalling pathway can be regarded as a promising target to control viral infections. This review discusses the dynamic interactions between the NFAT signalling pathway and viral pathogens. It also addresses several drugs and agents that can target the NFAT signalling pathway at different levels to control viral infections.

Long-COVID affects a significant number of COVID-19 survivors, profoundly impacting daily life and work. Although research suggests a potential link between antibody levels and long-COVID risk, findings remain inconclusive. Understanding antibody dynamics could support the identification of patients at risk, improve long-COVID diagnosis, and guide protective strategies such as vaccination. Despite growing evidence, no systematic review has yet evaluated the current literature on this topic. We therefore aimed to synthesise and evaluate existing evidence on the association between anti-SARS-CoV-2 antibody titres and long-COVID, with the goal of clarifying their potential role in predicting long-COVID risk, guiding patient management, and informing future research directions. Studies published in PubMed/Medline databases between January 2020 and October 2024 were included without language restrictions. Studies on body fluids other than serum/blood were excluded. Study selection and quality assessment was conducted independently by two researchers. After screening 949 studies, 58 studies encompassing 53,739 individuals, and 7812 long-COVID patients, were included. Evidence was highly heterogenous but most studies reported an association between anti-SARS-CoV-2-spike antibodies and long-COVID, although the nature of the association appeared to be dependent on time from acute infection. Low anti-SARS-CoV-2-spike antibodies during acute COVID-19 were associated with increased risk of long-COVID. The association between low anti-SARS-CoV-2-spike antibodies during acute COVID-19 and long-COVID suggests that maintaining sufficiently high antibody levels may be protective. However, the current evidence level is low and further studies with sufficient power are required to confirm this association and to potentially determine protective cutoffs.

Arboviruses currently are regarded as a major worldwide public health concern. The clinical outcomes associated with this group of viruses may vary from asymptomatic infections to severe forms of haemorrhagic fever characterised by bleeding disorders. Similar to other systemic viral infections, arboviruses can either directly or indirectly affect different parts of the body, such as the urogenital system. The human urogenital system anatomically consists of two major subdivisions: (i) the urinary system, including the kidneys, ureters, bladder, and urethra, which plays a significant role in osmoregulation, control of blood volume, pressure, and PH, absorption/excretion of different ions, and toxin metabolism, and (ii) the genital system, composed of the prostate, uterus, testes, ovaries, penis, and vagina, which are responsible for reproductive functions. Arboviruses can impair normal urogenital system functions by direct viral pathogen activity, systemic forms of inflammation, haemorrhagic events and related dysfunctions, and the nephrotoxic side effects of specific medications employed for treatment leading to various urogenital disorders. The present review provides an overview of the potential capacity of two main arboviruses, known as Zika and dengue viruses, to affect the urogenital system. Moreover, it addresses Zika virus as a potential therapeutic oncolytic virus for urogenital cancers.