Emerging Microbes & Infections最新文献

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.

In Switzerland, thirteen-valent pneumococcal conjugate vaccine (PCV13) has been introduced in 2011. During the COVID-19 pandemic, cases of invasive pneumococcal disease (IPD) have decreased but consequences on the serotype epidemiology are less clear. The objective of the study has been to analyse the impact of PCV13 introduction and the COVID-19 pandemic on the IPD epidemiology and investigate the changes in the case fatality risk (CFR). We analysed data from the Swiss nationwide surveillance for the period 2012-2022. Poisson and logistic regression analyses were performed allowing us to inspect trends over time and to define serotypes that are associated with case fatality. In total, 8747 IPD cases were included from 2012 to 2022. IPD incidence dropped in the years 2020 (6.0/100,000) and 2021 (5.5/100,000) but recovered in 2022 (9.1/100,000). While the incidence numbers of patients >65 years did not reach the pre-pandemic level, numbers significantly increased in infants <1 year in 2022 (IRR 1.08, 95%CI: 1.01-1.16). The incidence of PCV13 serotypes among all IPD cases decreased until 2019 before increasing again during the pandemic (in 2022). Logistic regression analyses revealed that the PCV20 serotype 11A (OR: 1.76, 95%CI: 1.14-2.64), and the PCV13 serotypes 3 (OR: 1.26, 95% CI: 1.04-1.53) and 19F (OR: 1.76, 95%CI: 1.14-2.65) were significantly associated with increased CFR. In conclusion, the COVID-19 pandemic has had only minor temporary effects on the serotype distribution. Continued use of vaccines with extended serotype coverage may further reduce IPD disease burden and mortality.

Avian influenza A(H9N2) has been circulating in poultry across Asia, the Middle East, and Africa, posing human health risks. In Ghana, it has co-circulated among poultry with influenza A (H5N1). This report describes Ghana's first confirmed human case of avian influenza A(H9N2) virus infection in a two-year-old boy from Upper East Region, identified through active respiratory surveillance. Molecular and genomic analyses confirmed the virus was of the G1 lineage, closely related to other West African strains, with mammalian adaptive mutations known to increase human infection potential. The child experienced mild symptoms, received outpatient care, and recovered. Health authorities conducted epidemiological investigations. No source was identified for the child's infection; no additional human infections were detected. This case highlights the importance of robust avian influenza surveillance in animals and humans, particularly in regions with human-animal interactions. It underscores the importance of national and global collaboration using a One Health approach to detect and prevent zoonotic spillovers and potential pandemics.

During the COVID-19 pandemic, healthcare systems worldwide faced severe strain. This study, utilizing wastewater virus surveillance, identified that periodic spontaneous avoidance behaviours significantly impacted infectious disease transmission during rapid and intense outbreaks. To incorporate these behaviours into disease transmission analysis, we introduced the Su-SEIQR model and validated it using COVID-19 wastewater data from Beijing and Hong Kong. The results demonstrated that the Su-SEIQR model accurately reflected trends in susceptible populations and confirmed cases during the COVID-19 pandemic, highlighting the role of spontaneous collective avoidance behaviours in generating periodic fluctuations. These fluctuations helped reduce infection peaks, thereby alleviating pressure on healthcare systems. However, the effect of these spontaneous behaviours on mitigating healthcare overload was limited. Consequently, we incorporated healthcare capacity constraints into the model, adjusting parameters to further guide population behaviours during the pandemic, aiming to keep the outbreak within manageable limits and reduce strain on healthcare resources. This study provides robust support for the development of environmental and public health policies during pandemics by constructing an innovative transmission model, which effectively prevents healthcare overload. Additionally, this approach can be applied to managing future outbreaks of unknown viruses or "Disease X".

Yersinia pestis, the etiological agent of the devastating plague, has caused three pandemics in human history. While known for its fatality, it has long been intriguing that biovar microtus strains are highly attenuated to humans. The survival and replication within macrophages are critical in the early stages of the Y. pestis lifestyle within warm-blooded hosts. Here, we demonstrate that a frameshift truncation of gppA, a gene encoding the phosphohydrolase GppA that responsible for the conversion of stringent response alarmone pppGpp to ppGpp, significantly promotes Y. pestis to survive inside human macrophages. This frameshift mutation of gppA is present in all the evolutionary branches formed by the modern Y. pestis strains responsible for the plague pandemics, while the relative ancient microtus strains express a functional GppA showing high activity in catalyzing pppGpp to ppGpp conversion. This adaptive evolution potentially explains why microtus Y. pestis strains exhibit attenuated virulence in humans in contrast to the lethal pathogenicity of non-microtus strains. Transcriptome analysis suggests that the disturbed balance of the ratio of ppGpp to pppGpp caused by GppA inactivation results in an upregulation of genes involved in the synthesis of branched-chain amino acids, which are essential for bacterial growth. This enhanced survival ability within macrophages could be a key factor for the virulence of Y. pestis towards humans. Our work sheds light on the molecular mechanisms behind Y. pestis host-specific pathogenicity, offering significant implications for enhancing our ability to predict and counteract the emergence of new infectious diseases.