Current opinion in virology最新文献

Viral infections, including those affecting the respiratory tract, can alter the composition of the intestinal microbiota, which, in turn, can significantly influence both innate and adaptive immune responses, resulting in either enhanced pathogen clearance or exacerbation of the infection, possibly leading to inflammatory complications. A deeper understanding of the interplay between the intestinal microbiota and host immune responses in the context of respiratory viral infections (i.e. the gut–lung axis) is necessary to develop new treatments. This review highlights key mechanisms by which the intestinal microbiota, including its metabolites, can act locally or at distant organs to combat respiratory viruses. Therapeutics aimed at harnessing the microbiota to prevent and/or help treat respiratory viral infections represent a promising avenue for future investigation.

Virus infection activates specific pattern recognition receptors and immune signal transduction, resulting in pro-inflammatory cytokine production and activation of innate immunity. We describe here the molecular organization of early signaling pathways downstream of viral recognition, including conformational changes, post-translational modifications, formation of oligomers, and generation of small-molecule second messengers. Such molecular organization allows tight regulation of immune signal transduction, characterized by swift but transient responses, nonlinearity, and signal amplification. Pathologies of early immune signaling caused by genomic mutations illustrate the fine regulation of the immune transduction cascade.

Bacille Calmette-Guérin (BCG) remains the sole licensed vaccine against tuberculosis (TB), despite its variable efficacy in protecting against pulmonary TB. The development of effective TB vaccines faces significant challenges, marked by the absence of validated correlates of protection and predictive animal models. Strategic approaches to enhance TB vaccines and augment BCG efficacy include utilising prime-boost strategies with viral-vectored vaccines and exploring innovative delivery techniques, such as mucosal vaccine administration. Viral vectors offer numerous advantages, including the capacity to accommodate genes encoding extensive antigenic fragments and the induction of robust immune responses. Aerosol delivery aligns with the route of Mycobacterium tuberculosis infection and holds the potential to enhance protective mucosal immunity. Aerosolised viral-vectored vaccines overcome anti-vector immunity, facilitating repeated aerosol deliveries.

Influenza A virus (IAV) infections pose a global health challenge that necessitates a comprehensive understanding of the host immune response to devise effective therapeutic interventions. As monocytes and macrophages play crucial roles in host defence, inflammation, and repair, this review explores the intricate journey of these cells during and after IAV infection. First, we highlight the dynamics and functions of lung-resident macrophage populations post-IAV. Second, we review the current knowledge of recruited monocytes and monocyte-derived cells, emphasising their roles in viral clearance, inflammation, immunomodulation, and tissue repair. Third, we shed light on the consequences of IAV-induced macrophage alterations on long-term lung immunity. We conclude by underscoring current knowledge gaps and exciting prospects for future research in unravelling the complexities of macrophage responses to respiratory viral infections.

Respiratory viral infections represent a constant threat for human health and urge for a better understanding of the pulmonary immune response to prevent disease severity. Macrophages are at the center of pulmonary immunity, where they play a pivotal role in orchestrating beneficial and/or pathological outcomes during infection. Eicosanoids, the host bioactive lipid mediators, have re-emerged as important regulators of pulmonary immunity during respiratory viral infections. In this review, we summarize the current knowledge linking eicosanoids' and pulmonary macrophages' homeostatic and antimicrobial functions and discuss eicosanoids as emerging targets for immunotherapy in viral infection.

Human immunodeficiency virus-1 remains a major global health threat. Since the virus is often transmitted through sexual intercourse and women account for the majority of new infections within the most endemic regions, research on mucosal immunity at the female reproductive tract (FRT) is of paramount importance. At the FRT, there are intrinsic barriers to HIV-1 infection, such as epithelial cells and the microbiome, and immune cells of both the innate and adaptive arms are prepared to respond in case the virus overcomes the first line of defense. In this review, we discuss recent findings on FRT mucosal mechanisms of HIV-1 defense and highlight research gaps. While defense from HIV-1 infection at the FRT has been understudied, current and future research is essential to develop new therapeutics and vaccines that can protect this unique mucosal site from HIV-1.

Influenza virus is an important human pathogen with significant pandemic potential. Tissue-resident memory T cells (Trm) in the lung provide critical protection against influenza, but unlike Trm at other mucosal sites, Trm in the respiratory tract (RT) are subject to rapid attrition in mice, mirroring the decline in protective immunity to influenza virus over time. Conversely, dysfunctional Trm can drive fibrosis in aged mice. The requirement for local antigen to induce and maintain RT Trm must be considered in vaccine strategies designed to induce this protective immune subset. Here, we discuss recent studies that inform our understanding of influenza-specific respiratory Trm, and the factors that influence their development and persistence. We also discuss how these biological insights are being used to develop vaccines that induce Trm in the RT, despite the limitations to monitoring Trm in humans.

Mucosal tissues are frequent targets of both primary and metastatic cancers. This has highlighted the significance of both innate and adaptive anti-cancer immunity at mucosal sites. Trained innate immunity (TII) is an emerging concept defined as enhanced reactivity of innate leukocytes long after a previous stimulation that induces prolonged epigenetic, transcriptional, and metabolic changes. Trained innate leukocytes can respond to heterologous targets due to their lacking of antigen-specificity in most cases. Emerging experimental and clinical data suggest that certain microbes or their products induce TII in mucosal-associated innate leukocytes which endows heterologous anti-tumor innate immunity, in both prophylactic and therapeutic scenarios. In this mini-review, we summarize updated findings on the significance of TII in mucosal cancers. We also attempt to raise a few key questions critical to our further understanding on the roles of TII in mucosal cancers, and to the potential application of TII as anti-cancer strategy.

An estimated 257 million people are chronic carriers of hepatitis-B virus (HBV) infection, which resulted in around 1 million deaths, mainly due to hepatocellular carcinoma (HCC). Long-term nucleotide analog treatment of HBV infection is associated with favorable prognosis, no disease progression, and a reduction of HCC risk, but lifelong treatments are required. A better understanding of HBV replication cycle and the host immune response will likely improve the identification of new targets for drug development. Studies are ongoing to determine if it is possible to successfully combine direct-acting antivirals (DAA) with an immunomodulatory therapy to allow increased cure rates. This review will start with summarizing the HBV replication cycle, recall current treatments, and then discuss potential targets and antiviral approaches in development to optimistically reach the HBV cure.

Over the last decade, the emergence of several zoonotic viruses has demonstrated that previously unknown or neglected pathogens have the potential to cause epidemics and therefore to pose a threat to global public health. Even more concerning are the estimated 1.7 million still-undiscovered viruses present in the natural environment or ‘global virome’, with many of these as-yet uncharacterized viruses predicted to be pathogenic for humans. Thus, in order to mitigate disease emergence and prevent future pandemics, it is crucial to identify the global extent of viral threats to which humans may become exposed. This requires cataloguing the viruses that exist in the environment within their various and diverse host species, and also understanding the viral, host, and environmental factors that dictate the circumstances that result in viral spillover into humans. We also address here which strategies can be implemented as countermeasure initiatives to reduce the risk of emergence of new diseases.