Emerging Microbes & Infections最新文献

Buruli ulcer (BU) is a chronic and debilitating skin disease caused by the environmental pathogen, Mycobacterium ulcerans (MU). The primary virulence determinant is mycolactone, a cytotoxic lipid compound unique to MU and its other mycolactone producing mycobacteria (MPM) ecological variants. Although BU prevalence is highest in West Africa and Australia, little is known about MU and other MPM distribution in non-endemic regions such as the Southeastern United States (US). In this study, environmental samples (water filtrand, plant biofilm, soil, aquatic invertebrates) were collected from nine freshwater sites across Louisiana, Mississippi and Alabama over three sampling periods (August 2020, November 2020, March 2021). Samples were screened for MU and MPM presence and abundance by PCR and genotyped using variable number tandem repeat (VNTR) profiling. All nine sites were positive for MU or other MPM DNA in at least one substrate, except invertebrates. Overall, mean concentrations were 4.3 × 10⁴ genome units (GU)/sample in August 2020, 1.26 GU/sample in November 2020, and 55.5 GU/sample in March 2021. Profiling by VNTR identified four MU (designated A-D) and one M. liflandii genotype(s), among environmental samples, with genotype frequencies varying by site and sampling time. Detection of MU and M. liflandii genotypes in Southeastern US aquatic environments, matching those from BU endemic regions, provides rationale for ongoing surveillance. Our findings broaden the known geographic range of MU and MPMs and offer baseline data to help predict and prevent and predict the possibility of zoonotic transmission in Southeastern US.

Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints - providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses - two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines.Trial registration: ClinicalTrials.gov identifier: NCT01799954..Trial registration: ClinicalTrials.gov identifier: NCT02109354..Trial registration: ClinicalTrials.gov identifier: NCT02404311..Trial registration: ClinicalTrials.gov identifier: NCT02207920..Trial registration: ClinicalTrials.gov identifier: NCT02296541..Trial registration: ClinicalTrials.gov identifier: NCT03284710..Trial registration: ClinicalTrials.gov identifier: NCT02915016..Trial registration: ClinicalTrials.gov identifier: NCT02997969..Trial registration: ClinicalTrials.gov identifier: NCT03122223..Trial registration: ClinicalTrials.gov identifier: NCT03409276..Trial registration: ClinicalTrials.gov identifier: NCT02968849..Trial registration: ClinicalTrials.gov identifier: NCT03060629..Trial registration: ClinicalTrials.gov identifier: NCT00223080..

The multiple epidemics of Zika virus (ZIKV) posed a substantial threat to public health. Clinical evidence suggests that ZIKV could break through the blood-brain, blood-placenta, and blood-testis barriers, leading to severe outcomes such as congenital malformations in newborns and Guillain-Barré syndrome in adults. Currently, there are no specific treatments for ZIKV infection. To address the antibody-dependent enhancement (ADE) of dengue virus (DENV) infection induced by ZIKV vaccination, we designed two modified prM-E RNAs (ZA and ZB) with specific mutations either shielding or disrupting the conserved fusion-loop epitope in the E protein. Then, we chose the mRNA-LNP vaccine platform to evaluate the safety and efficacy. After prime-boost immunization, ZA vaccine could induce high levels of T cells secreting IFN-γ and exhibit limited neutralizing ability against Asian-lineage and African-lineage ZIKV. After ZIKV challenge, ZA vaccine could provide complete protection in immunocompromised AG129 mice at low levels of neutralizing antibodies, preventing viral dissemination to the brain, uterus, and testes. Importantly, the ZA vaccine also reduced the ADE effect of DENV infection. Although ZB vaccine exhibited good immunogenicity, it could not achieve complete viral clearance in AG29 mice. Our findings suggested that the ZA vaccine could prevent both lethal ZIKV infection and DENV ADE induced by infection or vaccination.

In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.4.4b infection. The viral genome sequences are closely related to recent SD cattle H5N1 sequences. Cat H5N1 genomes had unique mutations, including T143A in haemagglutinin, known to affect infectivity and immune evasion, and two novel mutations in PA protein (F314L, L342Q) that may affect polymerase activity and virulence, suggesting potential virus adaptation. Dead cats showed systemic infection with lesions and viral antigens in multiple organs. Higher viral RNA and antigen in the brain indicated pronounced neurotropism. Lectin-histochemistry revealed widespread co-expression of sialic acid α-2,6 and α-2,3 receptors, suggesting cats could serve as mixing vessels for reassortment of avian and mammalian influenza viruses. No differences in clade 2.2 or 2.3.4.4b H5 pseudoviruses binding to cat lung/brain tissues indicated the neurotropism is unlikely mediated by receptor binding affinity.

Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice. Mice with enhanced antibody responses targeting conformational non-RBD region show better performance in cross-neutralization against the Wuhan-01, Delta, and Omicron subvariants. Via analyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of high ratio of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides new insight into overcoming the immune escape of SARS-CoV-2 variants.

We read with great interest the recent article by Wang et al. on peripheral nerve injury (PNI) associated with Japanese encephalitis virus (JEV) infection in high-endemic regions of China. The study provides important insights into the significant relationship between JEV infection and PNI, particularly highlighting clinical manifestations such as acute flaccid paralysis and respiratory muscle paralysis. While we commend the authors' work, we suggest caution in interpreting the findings due to several limitations. First, genotype-specific differences, notably between GIb and GIII strains, may influence disease severity, clinical progression, and prognosis, warranting further investigation for personalized management. Second, although adjustments were made for certain demographic and epidemiological variables, additional confounders such as vaccination status, environmental conditions, and socioeconomic factors should be incorporated to strengthen the robustness of future analyses. Third, reliance on surveillance data introduces potential biases due to incomplete or inaccurate reporting, especially in rural or underserved populations. Enhanced data collection methods, including digital health tools and standardized questionnaires, could improve accuracy and comprehensiveness. Beyond methodological considerations, the study underscores the importance of early diagnosis, biomarker development, and multidisciplinary collaboration in mitigating neurological complications of JEV. Strengthening vaccination coverage, particularly in remote regions, and expanding health education are also critical to reducing disease burden. Overall, this research advances understanding of JEV-associated PNI and highlights avenues for future studies to refine diagnostic, preventive, and therapeutic strategies that will improve long-term patient outcomes.

Japanese encephalitis virus (JEV) genotype IV (GIV) is one of the least common and most neglected genotypes worldwide, having been identified only on a few Indonesian islands until it was recently found to be the cause of outbreaks that occurred in several Australian states in early 2022. Given the limited availability of information, the vector range for JEV GIV remains unknown; thus, understanding this range could prove invaluable for future prevention efforts in new areas. Herein, we experimentally exposed four mosquito colonies originated from various countries with no previous reports of GIV to JEV GIV strain 19CxBa-83-Cv, which was isolated from Culex vishnui Theobald collected in Bali in 2019. At 7 and 14 days post-JEV GIV exposure through a membrane feeding method, mosquito bodies, head-wings-legs, and saliva were harvested for infection, dissemination, and transmission efficiency analyses. The results showed robust transmission efficiencies of the virus by Culex tritaeniorhynchus Giles (∼74%) and Aedes albopictus Skuse (∼52%) from Japan, followed by Culex quinquefasciatus Say from Vietnam (∼35%) and Culex pipiens form molestus from Turkey (∼18%). Although significant differences were observed, we found that the four mosquito species could transmit JEV GIV. The efficiency of biological transmission of this restricted genotype by mosquitoes from various origins suggests that these mosquito species could support localized transmission if the genotype were introduced to their respective areas. This study emphasizes the importance of remaining vigilant and continuing arbovirus surveillance in all locations.

N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotic RNA and is also present in various viral RNAs, where it plays a crucial role in regulating the viral life cycle. However, the molecular mechanisms through which viruses regulate host RNA m6A methylation are not fully understood. In this study, we reveal that SARS-CoV-2 and HCoV-OC43 infection enhance host m6A modification by activating the mTORC1 signalling pathway. Specifically, the viral non-structural protein nsp14 upregulates the expression of S-adenosylmethionine synthase MAT2A in an mTORC1-dependent manner. This mTORC1-MAT2A axis subsequently stimulates the synthesis of S-adenosylmethionine (SAM). The increase of SAM then enhances the m6A methylation of host RNA and facilitates viral replication. Our findings uncover a molecular mechanism by which viruses regulate host m6A methylation and provide insights into how SARS-CoV-2 hijacks host cellular epitranscriptomic modifications to promote its replication.

We present the first documented case of highly pathogenic avian influenza virus (HPAIV) subtype H5N5 in an Atlantic walrus (Odobenus rosmarus rosmarus). The animal was found dead in Svalbard, Norway, in 2023. Sequence analysis revealed the highest genetic similarity with virus isolates from different avian hosts.