Emerging Microbes & Infections最新文献

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.

Mucosal immunity is crucial for preventing the infection and transmission of respiratory viruses. Nasal antibody is inversely correlated with a lower risk of infection with respiratory viruses. However, the current reference standard for nasal antibody assessment is serum-based, mainly consisting of monomeric IgG and IgA. The applicability of serum-derived standards for assessing nasal antibodies, consisting mostly of dimeric or polymeric secretory IgA (sIgA), remains unvalidated. Herein, we first proved that the sera-derived standard was not applicable for assessing nasal antibodies. Using a non-homologous standard as a calibrator introduced systematic error up to 10 times, which did not benefit the understanding of mucosal antibody response. Therefore, we attempted to develop two candidate standards (CS1, CS2) using nasal mucosal lining fluids (NMLFs) collected from SARS-CoV-2 Omicron convalescents or intranasal vaccine recipients, and CS3 using a sIgA monoclonal antibody. CS2 exhibited broad-spectrum binding activity against 12 SARS-CoV-2 strains, including all tested Omicron subvariants. A collaborative study conducted by seven laboratories demonstrated that CS2 improved the harmonization of inter-laboratory variability (pre-standardization geometric coefficients of variance, 14-314%; post-standardization, 3-35%). Using CS2 ensured an accurate assessment of nasal antibodies. Thus, CS2 was established as a national standard for evaluating nasal SARS-CoV-2-specific antibodies (Lot: 300052-202401, 1000 U/mL). Our work provides a benchmark for evaluating mucosal vaccines for SARS-CoV-2 and inspires new avenues for developing new reference standards for other mucosal vaccines.

We previously observed a notable discrepancy in the distribution of HEV-3 subtypes between wastewater and clinical samples in Sweden. To confirm this observation and comprehensively elucidate HEV-3 circulation patterns across humans, animals, and environmental waters in Sweden, we analysed the HEV genetic diversity in archived wastewater samples between late 2016 and early 2018, clinical cases between 2012 and 2024, and all available Swedish sequences from the NCBI Virus database. HEV RNA was detected in all archived wastewater samples, with subtype 3c being the only subtype identified. In typed clinical cases, subtypes 3f (45/126) and 3c (44/126) were nearly equally distributed, though regional dominance varied. When incorporating human sequences from other Swedish studies, subtype 3f became dominant (75/168). Analysis of all available sequences revealed that 3f (113/136) was the dominant subtype in Sus scrofa (pigs and wild boars), while 3c (30/33) was dominant in environmental waters. These findings highlight the complex transmission dynamics of HEV-3 in Sweden. The near-absence of 3c in Swedish domestic pigs and wild boars, despite its high proportion in clinical cases, raises the question about the source of human 3c infection. In addition, the near-exclusive detection of 3c in wastewater suggests potential differences in viral shedding, disease severity of HEV-3 subtypes, or alternative host sources. This study emphasizes the importance of integrated One Health surveillance to track HEV circulation across reservoirs.

Limited studies compared the effectiveness of nirmatrelvir/ritonavir and molnupiravir against a control group on post-COVID-19 conditions. Our study examined the association of nirmatrelvir/ritonavir and molnupiravir with post-acute mortality and hospitalizations among outpatients using real-world outpatient records of COVID-19 designated clinics in Hong Kong. This is an observational study using a target trial emulation framework, involving nirmatrelvir-ritonavir versus no antiviral treatment (Trial 1) and molnupiravir versus no antiviral treatment (Trial 2). Outcomes included post-acute mortality, all-cause hospitalization, and hospitalization due to 13 selected sequelae. Relative effectiveness was assessed by comparing the cumulative incidence between two groups, reported as relative risk (RR), along with risk differences (RD) during day 0-30, 31-180, and 181-360. After screening, 140,477 and 96,030 patients were included in Trial 1 and 2, respectively. Compared with no treatment, nirmatrelvir/ritonavir-treated patients exhibited a significantly lower risk of post-acute mortality (31-180 days: RR, 0.71; 95% CI, 0.54-0.96; RD, 0.20%; 181-360 days: RR, 0.64; 95% CI, 0.50-0.82; RD, 0.32%) and all-cause hospitalization (31-180 days: RR, 0.82; 95% CI, 0.76-0.88; RD, 1.11%; 181-360 days: RR, 0.83; 95% CI, 0.78-0.89; RD, 1.18%). Patients receiving molnupiravir had a lower risk of 30-day mortality, but no significant beneficial effect was observed for the post-acute outcomes. In conclusion, this study demonstrated the effectiveness of nirmatrelvir/ritonavir in reducing post-COVID-19 outcomes among outpatients. While we observed the short-term effectiveness of molnupiravir in reducing mortality, no protective effect on long-term post-COVID-19 outcomes was observed.