Reviews in Medical Virology最新文献

Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.

Merkel cell polyomavirus (MCPyV) is a significant contributor to the development of Merkel cell carcinoma (MCC), an aggressive skin cancer with high recurrence and a low survival rate. In fact, it is the deadliest skin cancer. The precise routes of transmission for MCPyV-positive MCC remain unclear, but several factors may trigger its development. Conventional treatments for MCC are not highly effective, especially in patients with metastasis, with a clear need for new treatment options. Gene-targeted therapies hold great promise for the treatment of MCC, including the use of siRNA and CRISPR/Cas (C/Cas) but critically none have yet been translated into clinical trials. Validating this approach is the fact that several siRNA products are already FDA licenced, while C/Cas has entered clinical trial, albeit for conditions other than MCC. There are many challenges that must be overcome to move from preclinical research to the clinic. In this review, we provide a comprehensive summary of the current understanding of MCC, with a particular focus on MCPyV-positive MCC, and the status of gene-targeted therapies. Additionally, we discuss the major obstacles that impede MCC research and explore future prospects.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection amongst all ages, causing a significant global health burden. Preventative and therapeutic options for RSV infection have long been under development, and recently, several widely-publicised vaccines targeting older adult and maternal populations have become available. Promising monoclonal antibody (mAb) and antiviral (AV) therapies are also progressing in clinical trials, with the prophylactic mAb nirsevimab recently approved for clinical use in infant populations. A systematic review on current progress in this area is lacking. We performed a systematic literature search (PubMed, Embase, Web of Science, ClinicalTrials.gov, EudraCT, ANZCTR-searched Nov 29th, 2023) to identify studies on all RSV-specific mAbs and AV therapies that has undergone human clinical trials since year 2000. Data extraction focused on outcomes related to the therapeutic efficacy and safety of the intervention on trial, and all studies were graded against the OCEBM Levels of Evidence Table. Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Of the mAbs reviewed, nirsevimab and clesrovimab hold considerable promise. The timeline for RSV-specific AV availability is less advanced, although EDP-938 and AK0529 have reported promising phase 2 efficacy and safety data. Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633.

Dengue is a rapidly spreading mosquito-borne viral disease, posing significant public health challenges in tropical and subtropical regions. This systematic review and meta-analysis aimed to evaluate the relationship between maternal dengue virus infection and adverse birth outcomes. A literature search was conducted in PubMed, Embase, and web of science databases until April 2024. Observational studies examining the association between laboratory-confirmed maternal dengue infection and adverse birth outcomes such as preterm birth, low birth weight (LBW), small for gestational age (SGA), stillbirth, and postpartum haemorrhage were included. Data were extracted, and risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to pool data in R software (V 4.3). Twenty studies met the inclusion criteria. The pooled prevalence of preterm birth among dengue-affected pregnancies was 18.3% (95% CI: 12.6%-25.8%), with an OR of 1.21 (95% CI: 0.78-1.89). For LBW, the pooled prevalence was 17.1% (95% CI: 10.4%-26.6%), with an OR of 1.00 (95% CI: 0.69-1.41). SGA had a pooled prevalence of 11.2% (95% CI: 2.7%-36.9%) and an OR of 0.93 (95% CI: 0.41-2.14). The prevalence of stillbirth was 3.3% (95% CI: 1.6%-6.8%), with significant associations found in some studies (RR: 2.67; 95% CI: 1.09-6.57). Postpartum haemorrhage had an OR of 1.97 (95% CI: 0.53-2.69). While maternal dengue infection was associated with a higher prevalence of preterm birth and LBW, the associations were not statistically significant. Significant associations were observed for stillbirth in specific studies. Further research with standardized methodologies is needed to clarify these relationships and identify potential mechanisms.

The aim of this systematic review and meta-analysis was to comprehensively evaluate the latest evidences and summarise the impact of HIV on PCI outcomes. A PRISMA guided literature search was conducted on 14 February 2024 in Web of Science, PubMed, Virtual Health Library, Google Scholar and Scopus. We searched with the term '("percutaneous coronary intervention" OR "PCI") AND ("human immunodeficiency virus" OR "HIV" OR "acquired immunodeficiency syndrome" OR "AIDS")' after selecting the keywords from randomly chosen included papers. We included 8 papers of 781 screened records. HIV (+) patients had significant in-hospital, 1-year and overall (event at the last follow up point) all-cause mortality compared to HIV (-) group (OR: 1.73, 95%CI: 1.57-1.90, p < 0.01), (OR: 1.39, 95%CI: 1.07-1.81, p = 0.01) and (OR: 1.69, 95%CI: 1.55-1.85, p < 0.01), respectively. HIV (+) patients had significantly higher odds of developing MACE (OR: 1.35, 95%CI: 1.12-1.62, p = 0.001) compared to the HIV (-) group. No differences between both groups were detected regarding in-hospital and overall CV mortality, TVR, TLR, post-PCI TIMI grade 3 flow, cerebrovascular accidents and recurrent coronary events (p > 0.05). Our study revealed that people with HIV who underwent PCI in this modern era may have worse short and long-term PCI outcomes. This finding highlights the need for specialised cardiovascular care protocols for the HIV population. However, enhanced clinical management and preventative measures are imperative to improve PCI success rates in patients with HIV.

Poxviridae is a diverse family of double-stranded DNA viruses, historically significant for diseases like smallpox caused by variola virus (VARV). These viruses exhibit unique cytoplasmic replication strategies, large genomes encoding numerous proteins, and the ability to cause severe cutaneous and systemic diseases. Recent attention has focused on their neurotropic potential, including mechanisms of CNS invasion, immune-mediated damage, and clinical manifestations such as encephalitis and myelitis. This review synthesises current knowledge on poxvirus neurotropism, highlighting pathophysiological mechanisms and clinical implications.

Neurotropic viruses have been implicated in altering the central nervous system microenvironment and promoting brain metastasis of breast cancer through complex interactions involving viral entry mechanisms, modulation of the blood-brain barrier, immune evasion, and alteration of the tumour microenvironment. This narrative review explores the molecular mechanisms by which neurotropic viruses such as Herpes Simplex Virus, Human Immunodeficiency Virus, Japanese Encephalitis Virus, and Rabies Virus facilitate brain metastasis, focusing on their ability to disrupt blood-brain barrier integrity, modulate immune responses, and create a permissive environment for metastatic cell survival and growth within the central nervous system. Current therapeutic implications and challenges in targeting neurotropic viruses to prevent or treat brain metastasis are discussed, highlighting the need for innovative strategies and multidisciplinary approaches in virology, oncology, and immunology.

Dengue is a disease caused by a flavivirus (DENV) and transmitted by the bite of a mosquito, primarily the Aedes aegypti and Aedes albopictus species. Previous studies have demonstrated a relationship between the host gut microbiota and the evolution of dengue. It seems to be a bidirectional relationship, in which the DENV can affect the microbiota by inducing alterations related to intestinal permeability, leading to the release of molecules from microbiota dysbiosis that can influence the evolution of dengue. The role of angiotensin II (Ang II) in the microbiota/dengue relationship is not well understood, but it is known that the renin-angiotensin system (RAS) is present in the intestinal tract and interacts with the gut microbiota. The possible effect of Ang II on the microbiota/Ang II/dengue relationship can be summarised as follows: the presence of Ang II induced hypertension, the increase in angiotensinogen, chymase, and microRNAs during the disease, the induction of vascular dysfunction, the production of trimethylamine N-oxide and the brain/microbiota relationship, all of which are elements present in dengue that could be part of the microbiota/Ang II/dengue interactions. These findings suggest the potential use of Ang II synthesis blockers and the use of AT1 receptor antagonists as therapeutic drugs in dengue.

A wide variety of inflammatory mediators, mainly cytokines and chemokines, are induced during SARS CoV-2 infection. Among these proinflammatory mediators, chemokines tend to play a pivotal role in virus-mediated immunopathology. The C-C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1) is a potent proinflammatory cytokine and strong chemoattractant of monocytes, macrophages and CD4+ T cells bearing C-C chemokine receptor type-2 (CCR2). Besides controlling immune cell trafficking, CCL2 is also involved in multiple pathophysiological processes including systemic hyperinflammation associated cytokine release syndrome (CRS), organ fibrosis and blood coagulation. These pathological features are commonly manifested in severe and fatal cases of COVID-19. Given the crucial role of CCL2 in COVID-19 pathogenesis, the CCL2:CCR2 axis may constitute a potential therapeutic target to control virus-induced hyperinflammation and multi-organ dysfunction. Herein we describe recent advances on elucidating the role of CCL2 in COVID-19 pathogenesis, prognosis, and a potential target of anti-inflammatory interventions.