Current topics in microbiology and immunology最新文献

The investigation and understanding of the immune response to dengue, including its protective and pathogenic functions, present unique challenges, particularly due to the circulation of four distinct serotypes. While infection with one serotype induces long-term protection, including some level of temporary cross-protection against other serotypes, epidemiological evidence suggests an increased risk of severe disease following subsequent heterologous infections. Although the antibody-mediated response has been more extensively studied in this context, it is also evident that T cell immunity contributes to infection resolution and long-term memory, but in some circumstances, it can influence immunopathology. In this chapter, we will present findings regarding T cell-specific DENV epitopes and activated T cell repertoire and discuss the role of distinct T cell subtypes and their functional association with protection, memory response, as well as how altered T cell responses can contribute to disease severity. A deeper understanding of these mechanisms is essential for elucidating disease pathogenesis and identifying key protection and disease markers, which are critical for the development and efficacy assessment of dengue vaccine. In addition, T cell-mediated immunity should be considered in the design and implementation of immunization programs.

Climate plays a crucial role in shaping dengue virus (DENV) transmission dynamics by influencing directly the physical and behavioural traits of mosquito individuals and viral replication. This chapter describes and evidences the intricate relationships between climate variables, mosquito traits and DENV transmission, highlighting the importance of understanding such connections in the context of a growing DENV burden and a global environmental change.

Dengue is the most important viral disease transmitted to humans by mosquitoes and is caused by the dengue virus (DENV), which belongs to the Orthoflavivirus genus within the Flaviviridae family. The DENV RNA genome encodes ten proteins: three structural (C, prM, and E) and seven nonstructural (NS1-NS5) proteins. A comprehensive understanding of DENV interactions with both mammalian and mosquito cells is essential for the development of specific antivirals, which are currently lacking. In this chapter, we provide an overview of the viral replicative cycle, with a strong emphasis on the viral RNA genome, the composition of the replicative complexes, and the replication mechanisms. In addition, we discuss DENV-induced remodeling of cellular membranes and cellular responses to infection. Finally, key knowledge gaps and research priorities in the study of virus-cell interactions are highlighted.

Dengue is a mosquito-borne viral disease that poses a global public health problem, particularly in tropical and subtropical regions. It is caused by the dengue virus (DENV), which comprises four antigenically distinct serotypes. The clinical manifestations of the disease overlap with those of other febrile diseases, including other arboviruses such as Zika and chikungunya, making clinical and epidemiological diagnosis difficult. Therefore, an accurate laboratory diagnosis is essential for effective clinical management, especially during the early stages of the disease, to prevent progression to severe forms.Over the years, significant advancements have been achieved in dengue diagnostics. This chapter provides a comprehensive overview of current diagnostic techniques, detailing their principles, applications, and limitations. It covers a range of methodologies, including virus isolation, nucleic acid amplification tests (NAATs), nonstructural protein 1 (NS1) antigen detection assays, immunohistochemistry, serological tests for IgM and IgG antibodies, and lateral flow point-of-care tests. Additionally, novel approaches such as multiplex platforms, next-generation sequencing (NGS), and biosensor-based tests are explored for their potential to address existing challenges and improve diagnostic accuracy.The choice of diagnostic strategy largely depends on the time course of infection and the available methodologies, resources, infrastructure, and technical expertise. Furthermore, the high degree of cross-reactivity between flaviviruses makes diagnosis by serological assays difficult, particularly in regions where multiple flaviviruses co-circulate. Dengue vaccination is also expected to influence the results of serological assays, requiring adjustments to algorithms and careful interpretation of results. By tailoring diagnostic approaches to local capabilities and accounting for the effects of vaccination, dengue diagnosis, and disease management can be improved.

This chapter offers an overview of dengue vaccines that have advanced to clinical trials, addressing the intricate challenges in their development. It details the complexities of the dengue virus, including its four serotypes and the phenomenon of antibody-dependent enhancement (ADE), which significantly impacts vaccine design. The chapter reviews the historical trajectory and current landscape of vaccine candidates, such as Dengvaxia^®, Qdenga^®, and Butantan-DV, analyzing their efficacy, safety profiles, and the lessons learned from their clinical trials. It also discusses other hurdles like suitable animal models and viral interference. Ultimately, the chapter highlights the advancements made and outlines future research directions crucial for a universally effective dengue vaccine.

Human papillomavirus (HPV) infection is the necessary cause of cervical cancer (CC) and other HPV-related malignancies, yet by itself is not sufficient for malignant progression. A myriad of co-factors influences the risk that an HPV infection persists and progress to precancerous lesions and invasive disease. Understanding these cofactors is crucial for risk stratification and informing comprehensive preventive strategies-complementing HPV vaccination and screening-to further reduce the incidence of cervical and other HPV-associated cancers.This chapter reviews the epidemiological and mechanistic evidence for key cofactors in HPV-driven carcinogenesis. The most established cofactors-including tobacco smoking, immunosuppression (particularly HIV infection), long-term use of oral contraceptives, high parity, and coinfection with other sexually transmitted infections-have consistently been associated with increased risk of HPV persistence and disease progression. We discuss their prevalence, magnitude of risk, and biological plausibility. Emerging and less established cofactors, such as the cervical microbiome, nutritional status and diet, and host genetic polymorphisms, which may modulate immune responses to HPV or the propensity for viral persistence are also explored.

This chapter discusses the role of DNA methylation, an epigenetic mechanism that regulates gene expression, as a key event in cervical carcinogenesis, and highlights its potential as a biomarker for detecting cervical cancer and high-grade precancerous lesions. Methylation levels of specific genes (methylation markers) gradually increase with cervical disease severity, allowing several clinical applications. Methylation markers have been evaluated as alternative triage tools for high-risk (hr) human papillomavirus (HPV)-positive women, including those with borderline or mildly abnormal cytology results, and for use in specific populations such as women living with HIV. Methylation testing often outperforms traditional cytology-based triage methods and offers long-term reassurance against cervical cancer when the result is negative. Additionally, methylation markers have shown prognostic potential in predicting the natural course of high-grade precancerous lesions, as well as a promising performance for the detection of recurrent disease. While ongoing research focuses on validating methylation testing in self-collected samples, low-resource settings, and HPV-vaccinated populations, current evidence supports its potential to enhance early detection, risk stratification, and post-treatment monitoring in cervical cancer prevention and care.

Human papillomavirus (HPV) vaccination effectively reduces the risk of HPV-attributable cancers, including cervical, vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers. Concerns for a lower-than-expected vaccine impact, as defined as an increase in the prevalence of precancer by nonvaccine types, compared to that anticipated based on attribution studies, have been raised in the postvaccination era. Three distinct and nonmutually exclusive processes-HPV type replacement, clinical unmasking, and viral unmasking-could be responsible for this apparent increase of nonvaccine types. HPV type replacement, in which nonvaccine types fill a niche left vacant after the elimination of vaccine types, is unlikely to occur due to the remarkable genetic stability of the virus and the lack of natural competition between individual HPV types. However, clinical unmasking, in which the absence of clinical interventions aimed at eliminating cervical disease caused by vaccine types permits uninterrupted progression of nonvaccine types, may occur since HPV coinfections are common. Alternatively, the observed shift could be completely erroneous due to the false discovery of type replacement via viral unmasking, a diagnostic assay artifact. In this chapter, we describe these processes and the mechanisms underlying them.

Dengue is the most common arboviral infection in the world, causing up to 400 million cases per year. Although most cases are asymptomatic, the virus can cause a wide range of symptoms varying from high fever and pain, common to several arbovirus infections, to hemorrhagic fever and shock syndrome, which can often be fatal. Despite the association of some genotypes with disease severity, most symptom varieties can be traced to the interaction of the virus with the immune system. As early as viral entry, Dengue virus co-evolved with humans to evade the innate immune system, especially the antiviral response triggered by type I and III interferons, posing a strict bottleneck to its host range. This directly affects our ability to study the virus interaction with the innate immune system. Here, we will explore how dengue virus is recognized by pattern recognition receptors and triggers an immune response and how cells associated with innate immunity influence the course of infection, culminating with the inflammatory response, key to understanding the spectrum of dengue disease.