Reviews in Medical Virology最新文献

Dengue virus (DENV), a major arboviral pathogen of global concern, evolves rapidly through a combination of intrinsic molecular mechanisms, vector adaptation, and host immune pressures. Despite extensive research, major gap remains in understanding how these forces, collectively generate, shape, and fix adaptive mutations that drive DENV evolution. In this review, we explore the molecular mechanisms underlying DENV evolution, with emphasising the error-prone RNA-dependent RNA polymerase, template switching, recombination, and the modulatory effects of viral RNA secondary structures. We also highlight the replicase complex's intrinsic tolerance to mutations as a driver of evolutionary plasticity. At the protein level, we summarise adaptive mutation in capsid, envelop, NS1 and NS5 protein that influence virulence, transmission efficiency, and immune escape. Additionally, we also address the role of vector adaptation, whereby DENV overcomes midgut and salivary gland infection barriers in Aedes mosquitoes, often through bottleneck-driven selection and compensatory mutations, consequently enhancing transmission potential. Finally, we discuss host immune-driven selection including T cell-mediated immune responses, and the regulation of IFN, NF-κB, and PI3K/Akt/mTOR signalling pathways shapes the evolution of DENV. Together, these insights highlight the dynamic interplay between viral genetics, mosquito vectors, and host immunity in shaping the evolutionary trajectory of DENV.

The recent review by Yong et al. (Rev Med Virol. 2025; 35:e70070) proposes the entity of "Long Vax Syndrome" or Post-COVID-19 Vaccination Syndrome (PCVS). While this synthesis of anecdotal and early observational reports is a timely contribution, it necessitates a critical evaluation of the underlying evidence. This letter highlights substantial methodological limitations, including a reliance on data susceptible to significant ascertainment bias and the conflation of correlation with causation, given the non-negligible background prevalence of conditions like POTS and chronic fatigue. We argue that the pathophysiological narrative, while plausible, remains highly speculative due to a lack of direct mechanistic validation in human subjects. Furthermore, the proposed therapeutic strategies, borrowed from analogous disorders, are empiric and untested in this specific context, posing potential risks if adopted without evidence. The review by Yong et al. should thus serve not as a definitive guide, but as a critical catalyst for a disciplined research agenda. We outline essential next steps, including the urgent need for large, prospective controlled cohort studies to establish true incidence, deep phenotyping to identify distinct endotypes, and the development of standardised diagnostic criteria before randomised controlled trials can ethically evaluate interventions. Only through such rigorous inquiry can we ensure both compassionate care for affected individuals and the preservation of public confidence in vaccines.

Persistent high-risk Human Papillomavirus (HPV) infection causes anogenital and oropharyngeal cancers across all genders. The primary cancer associated with HPV is cervical cancer and the HPV vaccination before sexual exposure is recommended for cervical cancer elimination globally. This scoping review aims to map the preliminary evidence regarding the determinants of adolescent HPV vaccine acceptance and hesitancy during the COVID-19 pandemic in high income countries. A scoping review was conducted as per the updated Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Using the PCC (Population, Concept, and Context) framework, search keywords and search strategies were developed. Electronic databases were searched using specific search terms and the last search date noted as February 8, 2025. A thematic content analysis was carried out to identify the themes and subthemes by a deductive approach. Fourteen studies were included as the potential sources of evidence in this review. The study population included 493,819 adolescents from Australia, Hong Kong, Italy, Poland, Saudi Arabia, and the USA. The themes identified were inequity, attitude and behaviour, knowledge and communication, and engagement and influence. The COVID-19 pandemic generated a negative parental attitude towards HPV vaccines for a brief period. The adolescent HPV vaccine acceptance mainly depended on strong parental support and appropriate access to healthcare professionals and vaccination services. Travel restrictions, lockdowns, school closures, and social distancing contributed to significant HPV vaccine hesitancy in high income countries.

The recent outbreak of the Monkeypox (Mpox) virus has raised significant concerns. First identified in 1958, Monkeypox virus (MPXV) belongs to the Orthopoxvirus genus, sharing similarities with the Smallpox virus. It is a zoonotic disease mainly harboured by rodents and transmitted through direct interaction with infected animals, respiratory droplets, contaminated materials, or body fluids and from mother to child during pregnancy. The MPXV has a brick-shaped lipoprotein envelope, usually containing conserved genes essential for viral replication and variable genes that influence pathogenicity. The virus exists in two genetic clades: West African (Clade II) with lower mortality (∼1%) and Central African (Clade I) with higher mortality (∼10%). The spread of Mpox was primarily limited to Congo Basin (West Africa), which eventually increased globally. In the year 2022, World Health Organisation (WHO) declared Mpox an 'International Public Health Emergency Concern', indicating vital need to develop robust strategies to combat Mpox. As per 2022 outbreak, 40% patients required medical treatment (antiviral, antibacterials, and pain killer), 1%-13% patients required hospitalisation and 0.1% cases ended in fatality. The contemporary pre- and post-prophylactic therapies, include non-replicating modified vaccinia Ankara vaccination, are not yet available in endemic countries in Africa. Moreover, since January 1, 2024, there have been 812 deaths reported linked to the clade Ib Mpox outbreak in Central Africa, mostly in the Democratic Republic of the Congo. This corresponds to a case-fatality rate of about 3% among the nearly 29,000 assumed cases by September 2024. Hence, this review outlines routes of Mpox transmission and early and chronic symptoms of infection. The mechanisms employed by the virus for immune evasion or immune suppression to promote viral survival inside the host are discussed in detail. The review illustrates Mpox therapeutics and medications, including anti-viral drugs that help to treat symptoms, prevent complications, and support recovery, particularly in the immunocompromised patients. In addition, we discuss recent advancements in the development of prophylactic vaccine for Mpox, including ACAM2000, LC16m8, JYNNEOS (MVA), and others. Future research directions include exploiting the conserved Mpox antigens to develop safer and more broadly protective vaccines. There is also an urgent need for international collaborations in surveillance, rapid response systems and comprehensive OMICS studies for understanding the viral evolution and mutations, which will greatly aid vaccine design and therapeutic strategies to combat Mpox.

Dengue virus (DENV) is an important human pathogen that infects millions of people each year and can cause diseases such as dengue haemorrhagic fever and dengue shock syndrome. Despite the efforts of the immune system to control the innate and adaptive immune responses to the virus, DENV escapes from immune responses using complex and multiple mechanisms. In certain cases, these immune evasion strategies may also contribute to the neurotropic potential of DENV, facilitating its ability to invade or affect CNS. This narrative review summarises the current knowledge by focusing on major immune evasion pathways of dengue virus at three levels of innate, adaptive and effector mechanisms, including inhibition of interferon production, disruption of immunological signalling pathways, regulation of proliferation proteins and inhibition of effector cells. The aim of this review is to collect, compare and describe all the ways in which this virus evades immunity, which will help identify knowledge gaps for future research and subsequently guide the development of effective vaccines and therapeutics.

Giant cell arteritis (GCA) is a systemic vasculitis of older adults with potential for severe ischaemic complications. Although its aetiology remains unclear, varicella zoster virus (VZV) has been proposed as a potential trigger due to its neurotropism and ability to induce granulomatous vasculitis. However, conflicting evidence has clouded this association. To systematically assess and synthesise the available evidence on the presence of VZV in arterial tissues of patients with GCA, and to evaluate the strength and consistency of this association. We conducted a systematic review and meta-analysis according to PRISMA guidelines. We searched Web of Science, PubMed, and Scopus (up to April 2025) for studies examining VZV detection in arterial tissues of GCA-positive and GCA-negative patients. Eligible studies reported original data using immunohistochemistry, PCR, or molecular methods. Pooled log odds ratios (LogORs) were calculated using a random-effects model. Heterogeneity, publication bias, subgroup effects (by geography), and study quality (NOS scores) were assessed. Eighteen studies met inclusion criteria, encompassing 606 GCA cases and 589 controls. Meta-analysis revealed a significant association between VZV presence and GCA (pooled LogOR: 1.03; 95% CI: 0.35-1.71; p = 0.003). Heterogeneity was moderate (I² = 38.7%). Sensitivity analyses confirmed robustness of the association. Subgroup analysis demonstrated a significant association in U.S.-based studies (LogOR: 1.86; 95% CI: 0.70-3.01), but not in European cohorts (LogOR: 0.09; 95% CI: -0.62-0.79; p for difference = 0.011). Egger's test suggested potential publication bias (p = 0.027). Meta-regression showed no significant relationship between study quality and effect size. Our findings indicate a statistically significant but heterogenous association between VZV and GCA. The signal appears geographically and methodologically dependent, with conflicting high-quality studies reporting both positive and null findings. While the data support further investigation into a potential viral role in GCA pathogenesis, current evidence does not justify routine antiviral treatment or changes in clinical practice. Future research should employ standardized, blinded, and multicenter approaches to clarify this potential link.

The gut virome, an integral but still poorly understood component of the gut microbiota, is emerging as an important player in the pathophysiology of irritable bowel syndrome (IBS). Recent evidence suggests that alterations in virome diversity and phage-bacteria interactions contribute to gut dysbiosis, immune modulation and gut barrier dysfunction in IBS. This review summarises current knowledge on virome alterations in IBS and emphasises the role of bacteriophages in shaping microbial ecology and host responses. Different virome signatures in the different subtypes of IBS highlight the potential of the virome for disease stratification and personalised therapeutic strategies. In addition, we discuss the analytical challenges in virome research and explore novel virome-targeted interventions, including phage therapy and dietary modulation. A deeper understanding of virome dynamics in the gut could open new avenues for precision medicine approaches to treat IBS.

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency, characterised by impaired antibody production, immune dysregulation, and a broad spectrum of clinical manifestations. Gastrointestinal involvement is frequent, affecting up to 20% of patients and significantly contributing to morbidity and mortality. Among infectious triggers, norovirus plays a particularly important role, as persistent infection may drive chronic inflammation and contribute to the development of CVID-associated enteropathy, a severe non-infectious complication marked by chronic diarrhoea, malabsorption, and weight loss. The pathogenesis is multifactorial, involving impaired humoural immunity, absent mucosal IgA, and aberrant T- and B-cell interactions, resulting in defective viral clearance and sustained mucosal injury. Although viral eradication has been shown to induce clinical and histological improvement, no standardized therapeutic strategy currently exists. Intravenous or subcutaneous immunoglobulin replacement fails to adequately protect against gastrointestinal infections, and off-label antivirals such as ribavirin, nitazoxanide, or interferon alpha have yielded inconsistent results. Oral administered immunoglobulin preparations have shown variable efficacy in case reports, reflecting differences in viral genotypes, host susceptibility, and donor antibody repertoires. In this review, we summarise current knowledge on the epidemiology, pathogenesis, clinical features, and diagnostic considerations of CVID-associated enteropathy linked to chronic norovirus infection, with a special focus on therapeutic aspects. We also present our experience with a patient successfully treated with immunoglobulin therapy administered via nasogastric tube, leading to clinical remission, nutritional recovery, and viral clearance. Recognising norovirus as a key etiological factor in CVID enteropathy emphasises the need to conduct systematic studies and evidence-based therapeutic approaches.

The eradication of HIV remains challenging, primarily due to the persistence of latent HIV reservoirs within the human body that evade immune detection, even in the context of effective antiretroviral therapy (ART). These reservoirs, principally comprising CD4+ T-cells, are characterised by their heterogeneity and dynamic nature, rendering their identification and targeted elimination ineffectual. This review examines recent advances in the identification of cell surface markers associated with HIV latency, emphasising their potential utility in the detection of HIV reservoir cells. Thus, markers such as CD2, CD20, CD30, CD32a, CD69, CD73, CD98, CD127, CD161, and VLA-4, amongst others, are presented herein and evaluated based on their roles in HIV infection dynamics, latency maintenance, and reactivation potential. While promising candidates such as CD32a and PD-1 demonstrate significant enrichment of HIV DNA and replication-competent provirus, observations remain inconsistent across studies, highlighting the need for further research. Additionally, this review introduces P-selectin glycoprotein ligand-1 (PSGL-1), a cell surface molecule extensively studied in relation to its role in inflammation, as a potential marker for HIV reservoir cells. By consolidating current evidence, this article revisits the intriguing realm of HIV reservoir cells and provides knowledge and a broader canvas for their identification via detection of specific cell surface molecules.