Current topics in microbiology and immunology最新文献

EBNA1 plays multiple important roles in EBV latent infection and has also been shown to impact EBV lytic infection. EBNA1 is required for the stable persistence of the EBV genomes in latent infection and activates the expression of other EBV latency genes through interactions with specific DNA sequences in the viral episomes. EBNA1 also interacts with several cellular proteins and cellular DNA sites to modulate multiple cellular pathways important for viral persistence and cell survival. These cellular effects are also implicated in oncogenesis, suggesting a direct role of EBNA1 in the development of EBV-associated tumours.

Epstein-Barr virus (EBV) is a very successful human pathogen, with ~95% seroprevalence worldwide (Mentzer et al, Nat Commun 13:1818, 2022). If contracted in early childhood, EBV infection is typically asymptomatic; however, infections in adolescence and adulthood can manifest as infectious mononucleosis (IM). The innate immune response is the first line of defense, and its function is critical for controlling EBV infection. During EBV infection, components of the virus, known as pathogen-associated molecular patterns (PAMPs), are recognized by germline-encoded pattern recognition receptors (PRRs). PRRs are found on both non-immune and immune cells including antigen-presenting cells, such as macrophages, monocytes, dendritic cells, natural killer (NK), and mast cells. PRRs are also found on B cells and epithelial cells, the primary targets of EBV infection. Without immune surveillance, EBV can transform cells inducing various malignancies. Conversely, a prolonged innate immune response can lead to chronic inflammation which increases the likelihood of cancer. This review discusses innate immune recognition of EBV and its associated diseases.

Epstein-Barr virus chiefly infects B cells and epithelial cells but is capable of infecting other cell types in the human host. Host cell entry is a complex process mediated by several viral glycoproteins that define tropism and mediate membrane fusion. This chapter will review what is known about the function of viral glycoproteins in the entry process, explore the nature of interactions between viral glycoproteins and host cell receptors, and highlight gaps in knowledge about the entry process that remain to be filled.

Convalescent plasma has increasingly been used to treat various viral infections and confer post-exposure prophylactic protection during the last decade and has demonstrated favorable clinical outcomes in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the recent COVID-19 pandemic. The pandemic has highlighted the need for cost-effective, accessible, and easy-to-use alternatives to conventional blood plasmapheresis techniques, allowing hospitals to become more self-sufficient in harvesting and transfusing donor plasma into recipients in a single setting. To this end, the use of a membrane-based bedside plasmapheresis device (HemoClear) was evaluated in an open-label, non-randomized prospective trial in Suriname in 2021, demonstrating its practicality and efficacy in a low-to middle-income country. This paper will review the use of this method and its potential to expedite the process of obtaining convalescent plasma, especially during pandemics and in resource-constrained settings.

Despite concerns about potential side effects, based both on historical experience with plasma products and more recent concerns about contemporary use of plasma, COVID-19 convalescent plasma has been shown to be a very safe product. Research early in the COVID-19 pandemic documented-among the very large population of convalescent plasma recipients in the US Convalescent Plasma Study component of the FDA-authorized Expanded Access Program-that the overall risk profile was no different than that seen for fresh frozen plasma, a product used routinely in medical practice. The safety of CCP was further demonstrated using real-world evidence, pragmatic trials, and formal randomized trials. The rates of all serious adverse events were very low, an especially impressive finding in light of the fact that nearly all safety data came from the use of COVID-19 convalescent plasma in patients who were hospitalized, were older, and/or had significant co-morbid cardiopulmonary and metabolic disorders. The well-known complications of blood and plasma transfusions-transfusion-associated circulatory overload and transfusion-related acute lung injury-were found with no higher incidence than with standard use of blood and plasma, nor was there evidence for antibody-dependent enhancement or increased incidence of thromboembolic events. The comprehensive safety profile derived from studies enrolling hundreds of thousands of recipients of COVID-19 convalescent plasma across the world should allay safety fears about the rapid deployment of convalescent plasma in future pandemics.

The twenty-first century has witnessed seven human viral pandemics. Approximately once every three to four years over the past quarter-century, the world has experienced a new viral epidemic that expanded well beyond its original national borders to become a pandemic. The probability that another pandemic caused by a previously unknown agent will occur in the near future is thus very high and public health agencies must prioritize mechanisms for detecting their first signals. At the onset of these recent pandemics, no specific therapeutic agent was available for any of the newly emergent pathogens. However, convalescent plasma therapy can be available as soon as there are survivors and is likely to be effective if used early and in sufficient strength. But for the three forms of passive antibody-convalescent plasma, monoclonal antibodies, and hyperimmune globulins-to be available and effective in a pandemic situation, careful strategic planning will be necessary. In the pre-pandemic period, we must reinforce the capacities of blood banks and plasma fractionating companies in the production and storage of their products; ensure that outpatient settings can provide intravenous products; educate providers in the proper use of plasma; and create a research infrastructure to examine the effectiveness of passive antibody products. Once a pandemic is underway, regulatory bodies should simplify the approval of research and emergency use protocols and develop treatment registries. Incentives for the rapid production of monoclonal antibodies and hyperimmune globulins will likely be required. A national resource to link providers with passive antibody products and national databases to monitor pandemic progress and pandemic treatment will permit the most effective allocation of pandemic-fighting resources. We cannot afford to wait until the next pandemic is upon us to respond. The time to strengthen clinical, research, and manufacturing infrastructure to permit us to be ready to confront the next new virulent pathogen is now.

This volume takes a broad overview of antibody-based therapies prior to and during the COVID pandemic and examines their potential use in future pandemics. Passive antibody therapy was the first effective antimicrobial treatment and its development in the early twentieth century helped catalyze immunological and microbiological research. During the era of serum therapy (1890-1940) antibody-based therapies were developed against both viral and bacterial diseases. Effective treatment required an understanding of how to quantify antibodies, how to develop serotype-specific sera and recognition of the need to treat early in disease. Thus, although the era of serum therapy essentially ended with the development of small molecule antimicrobial therapy in the 1940s, antibody-based therapies led to important new scientific understanding, while remaining in use for some toxin and venom-caused diseases and in the prevention of outbreaks of viral hepatitis. A renewed interest in antibody-based therapies was seen in the widespread deployment of convalescent plasma and monoclonal antibodies during the COVID-19 pandemic. Convalescent plasma will likely be the first specific therapy during outbreaks with new pathogens for which there is no other therapy. For all forms of antibody-based therapies, effectiveness relies on the key principles of antibody therapy, namely, treatment early in disease with preparations containing sufficient antibody specific to the microbe in question.

The human mycobiome refers to the fungal communities residing across body sites and plays pivotal roles in human health and disease. This chapter summarizes technical advances and current knowledge on the human mycobiome and discusses its clinical implications. Although high-throughput sequencing-based approaches have greatly improved the resolution of profiling fungal populations compared to the traditional culture-based methods, researchers should be aware of the inherent limitations of each approach and choose the most appropriate one or combination based on specific context of their study. We highlight the research progress on the composition of mycobiome and its cross talk with the host in the gastrointestinal tract, respiratory tract, oral cavity, genital tract, tumor tissues, and skin surface. The complex cross-kingdom interactions with bacteria and the emergence of new fungal pathogens-potentially driven by environment factors, emphasize the need to integrate mycobiome studies into broader microbial networks and the One Health frameworks. Together, this chapter underscores the potential of the human mycobiome as a diagnostic and therapeutic target in various diseases and advocates for interdisciplinary efforts to address the impact of fungi on human health.

Fungal infections pose an important threat to public health and food security, and with the rise in antifungal drug and fungicide resistance, we are faced with a global crisis. Currently, humanity is at an intersection of global climate change driving the expansion of species range distributions, emergence of novel pathogenic fungi, and changing at-risk populations. Here, we review the main mechanisms of antifungal drug and fungicide resistance, new drugs and mode-of-action drug classes, and future topics for risk reduction. We propose that integrating One Health and surveillance is a crucial first step in addressing this issue. Additionally, we emphasise that global collaboration among multiple stakeholders is essential to reverse the current upward trend in observed resistance. Finally, plant and medical mycologists can and should work together for the creation of a common language and antifungal stewardship plan.

Climate changes including rising temperatures and increasing severe weather events (e.g., hurricanes, flooding, and wildfires) are impacting Earth's ecosystems and increasing microbial threats to human health. Microbes in the environment, including bacteria and fungi, are adapting to new habitats and hosts in ways that may make them more disease-causing. Environmental fungi are particularly climate-sensitive, with optimal growth at cooler temperatures (25-30 °C) and with reproductive spore dispersal dependent on atmospheric conditions. While environmental fungi play a crucial role supporting plant growth and recycling nutrients in soils, some cause mild to severe infections in humans. Climate changes are expanding the geographic range of some disease-causing fungi, leading to increased fungal infections, particularly in the aftermath of natural disasters. Additionally, fungal adaptations to environmental stressors may make fungi more likely to cause disease, such as increased heat tolerance (survival at body temperature of 37 °C), or more difficult to treat, due to evolving drug resistance to environmental fungicides. Here, we explore how climate change and natural disasters impact fungal distribution, adaptation, and exposure to humans, highlighting fungal threats to human health. We propose strategies to mitigate these emerging challenges, emphasizing the collaborative and interdisciplinary efforts needed to protect human health in a changing climate.