Editor’s Choice articles are based on recommendations by the scientific editors of Microbes & Immunity from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.
Abstract: Rabies continues to pose a significant fatal zoonotic threat, with approximately 59,000 human deaths reported annually, despite the disease being mostly preventable through vaccination. Recently, several notable scientific advancements have been made, including the determination of the pre-fusion conformation of the rabies virus glycoprotein (RABV-G), structure-guided antigen design strategies to enhance immunogenicity, and the development of mRNA-lipid nanoparticle (LNPs) delivery platforms encoding RABV-G. Pre-clinical models have shown that these mRNA-LNPs platforms induce neutralizing antibody titers that are approximately ten-fold higher than those elicited by traditional inactivated vaccines. Heterologous prime-boost vaccination regimens integrating inactivated rabies virus with mRNA boosters have demonstrated synergistic efficacy, achieving 100% protection with evidence of potential durability in non-human primate models. However, several critical knowledge gaps remain, such as the structure of the full-length or ectodomain of pre-fusion RABV-G, the mechanisms underlying pH-driven conformational changes of RABV-G and its fusion process, the binding mechanisms of different viral receptors, and the induction of long-term protection. Future breakthroughs will hinge on integrating technological innovation with global accessibility to achieve the “Zero by 30” rabies elimination initiative. This requires coordinated efforts to translate cutting-edge research into scalable, affordable interventions that address both scientific challenges and public health gaps.
Correlation between varicella-zoster virus infection and cancer development: A comprehensive analysis
Abstract: Varicella-zoster virus (VZV) is a highly prevalent pathogen primarily recognized for causing chickenpox during primary infection, and herpes zoster (HZ), also known as shingles, upon reactivation. While post-infectious complications of VZV, such as encephalitis, pneumonia, and post-herpetic neuralgia, are well-established, recent large population-based studies suggest that HZ may increase the risk of occult cancers. This has sparked discussions on the need for cancer screening in patients with HZ to improve early diagnosis and prognosis. However, the specific types of cancers most strongly associated with VZV reactivation have not been systematically identified, and the subsequent cancer risk remains inconclusive. Emerging evidence suggests that VZV may also modulate key oncogenic pathways, such as the inhibition of apoptosis, alteration of cell cycle regulatory enzymes, and interference with immunosurveillance, which could potentially promote cancer development. These findings indicate that VZV’s role in cancer biology extends beyond merely increasing cancer risk and may involve direct cellular manipulation that facilitates oncogenesis. Understanding the interplay between VZV and cancer is critical for public health. Further exploration of the mechanisms of viral oncogenesis could provide valuable insights into how VZV contributes to cancer development and open avenues for targeted preventive and therapeutic strategies.
Microbial involvement in myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and disabling disease related to persistent fatigue, exercise intolerance, post-exertional malaise, cognitive dysfunction, and musculoskeletal/joint pain. Gastrointestinal comorbidities, including irritable bowel syndrome, have been reported in affected individuals, indicating a potential role of gut microbiota in disease progression. In this paper, bacterial and metabolomic dysbiosis in subjects with ME/CFS are reviewed, and phenotypic, microbial, and metabolic biomarkers specific to individual cohorts are also identified. Furthermore, microbiome fluctuations or metabolic endotoxemia are proposed as possible disorder biomarkers. Based on the fact that gut microbiota dysbiosis reverts to a state of eubiosis in long-term patients with this condition, it may be hypothesized that disease progression begins with the loss of beneficial gut microorganisms, particularly short-chain fatty acid producers, leading to more widespread gastrointestinal phenotypes that are subsequently reflected in plasma metabolite levels. These alterations, specific of each individual, thereby result in metabolic and phenotypic shifts and in ME/CFS.
Abstract: The amplification of anti-infective immunity against a wide spectrum of acute and chronic infections caused by various pathogens is mediated by RANTES/CCL5. This chemokine controls infections caused by viruses, bacteria, fungi, and protozoans. In addition, RANTES/CCL5 exhibits anti-cancer effects by increasing NK-cell activity and targeting tumors. RANTES/CCL5 acts by amplifying antigen-specific immunity on mucosal surfaces, programmed T-cell responses, cytotoxic T lymphocytes (CTL), B-cell activation, and antibody production. RANTES/CCL5 exerts its effects by binding to C-C receptors, thereby triggering JAK/STAT signaling and inducing the migration of lymphocytes, NK cells, and monocytes. In the brain, RANTES/CCL5 activates astrocytes and upregulates anti-inflammatory interleukin (IL)-10 expression. Inflammatory cytokines rapidly induce RANTES/CCL5 expression in fibroblasts, epithelial cells, and monocytes/macrophages. In T-cells, RANTES/CCL5 expression is mediated by translational control of the transcription factor RFLAT-1/KLF13, which is responsible for a 3-day delay in RANTES/CCL5 secretion after T-cell activation. A cell membrane multi-protein complex containing CFTR, EBP50, ezrin, and PKC is a dominant regulator of both RANTES/CCL5 and inflammatory cytokine expression. Treatment of a volunteer patient suffering from long COVID/vaccine injury with the ezrin peptide RepG3 alleviated symptoms, substantially reduced serum proinflammatory cytokines to normal levels, and enhanced the expression of RANTES/CCL5. The immune amplification activities of RANTES/CCL5 and the ezrin peptide RepG3 exhibit striking similarities. In contrast, the ezrin peptide RepG3 differs from RANTES/CCL5 in its ability to significantly inhibit the expression of proinflammatory cytokines IL-1β, IL-6, IL-8, IL-13, TNF-α, and proinflammatory chemokines MIP-1α and MIP-1β. The mechanism through which the ezrin peptide RepG3 enhances adaptive immunity likely involves its induction of systemic elevation of RANTES/CCL5 expression and the simultaneous inhibition of proinflammatory cytokine expression.