IntroductionSeasonal influenza virus infection during pregnancy poses significant risks to maternal and fetal health, contributing to adverse neurodevelopmental outcomes in offspring. This study investigates the impact of maternal infection with two highly pathogenic H1N1 influenza A virus (IAV) strains on hippocampal neurogenesis and glial reactivity in neonatal and juvenile mice.MethodsMice were infected with the mouse-adapted influenza virus strain A/WSN/33 (H1N1) or A/California/07/09 (H1N1)pdm09 in a sublethal dose 14 days after pregnancy manifestation. After birth, several pups were sacrificed, brains and hippocampi were isolated and used for RT-qPCR (the expression of IL-1β, iNOS, IFNG, IL-6, TNFa was assessed), immunohistochemistry and Western blot for markers of neural progenitors (Sox2, Sox11), mature neurons (NeuN), microglia (Iba1), and astrocytes (GFAP). Within 2 weeks after birth, the mortality and body weight dynamics change were monitored in the remaining pups.Results and discussionFindings reveal that maternal infection with H1N1wsn disrupts early neurogenesis, while infection with H1N1pdm09 induces region-specific reductions in neurogenesis and heightened glial reactivity in 14-day-old offspring. Increased expression of pro-inflammatory cytokines and factors, including IL-1β and iNOS, in neonatal brain tissue suggests that maternal immune activation mediates neurodevelopmental disruptions. Despite reduced Sox2+ and Sox11+ neural progenitor cells, NeuN expression remained stable, implying potential compensatory mechanisms. Elevated astrocyte reactivity in the CA1 and dentate gyrus regions highlights prolonged neuroinflammatory effects. These results underscore the role of maternal influenza-induced immune responses in shaping hippocampal development, with implications for long-term cognitive and behavioral outcomes. Understanding these mechanisms may inform strategies to mitigate neurodevelopmental risks associated with prenatal infections.
The COVID-19 pandemic and relevant non-pharmaceutical interventions (NPIs) interrupted the circulation of common respiratory viruses. These viruses demonstrated an unprecedented asynchronous resurgence as NPIs were relaxed. We compiled a global dataset from a systematic review, online surveillance reports and unpublished data from Respiratory Virus Global Epidemiology Network, encompassing 92 sites. We compared the resurgence timings of respiratory viruses within each site and synthesised differences in timings across sites, using a generalised linear mixed-effects model. We revealed a distinct sequential timing in the first post-pandemic resurgence: rhinovirus resurged the earliest, followed by seasonal coronavirus, parainfluenza virus, respiratory syncytial virus, adenovirus, metapneumovirus and influenza A virus, with influenza B virus exhibiting the latest resurgence. Similar sequential timing was observed in the second resurgence except influenza A virus caught up with metapneumovirus. The consistent asynchrony across geographical regions suggests that virus-specific characteristics, rather than location-specific factors, determining the relative timing of resurgence.
Respiratory viruses represent a significant public health threat. There is the need for robust and coordinated surveillance to guide global health responses. Established in 2012, the Global Influenza Hospital Surveillance Network (GIHSN) addresses this need by collecting clinical and virological data on persons with acute respiratory illnesses across a network of hospitals worldwide. GIHSN utilizes a standardized patient enrolment and data collection protocol across its study sites. It leverages pre-existing national infrastructures and expert collaborations to facilitate comprehensive data collection. This includes demographic, clinical, epidemiological, and virologic data, and whole genome sequencing (WGS) for a subset of viruses. Sequencing data are shared in the Global Initiative on Sharing All Influenza Data (GISAID). GIHSN uses financing and governance approaches centered around public-private partnerships. Over time, GIHSN has included more than 100 hospitals across 27 countries and enrolled more than 168,000 hospitalized patients, identifying 27,562 cases of influenza and 44,629 of other respiratory viruses. GIHSN has expanded beyond influenza to include other respiratory viruses, particularly since the COVID-19 pandemic. In November 2023, GIHSN strengthened its global impact through a memorandum of understanding with the World Health Organization, aimed at enhancing collaborative efforts and data sharing for improved health responses. GIHSN exemplifies the value of integrating scientific research with public health initiatives through global collaboration and public-private partnerships governance. Future efforts should enhance the scalability of such models and ensure their sustainability through continued public and private support.
BACKGROUND:Human parainfluenza viruses (hPIVs) are common viral causes of acute respiratory infections, resulting in substantial global disease burden. Seasonal patterns of hPIV epidemics can vary by geographical region and viral type, although these patterns are not well understood at a global level. We aimed to characterise regional and type-specific variations in hPIV seasonality and assess the potential role of climatic factors in explaining these variations. METHODS:In this systematic review and meta-analysis, we collected monthly aggregated seasonal activity data for hPIV and its four types (hPIV-1, hPIV-2, hPIV-3, and hPIV-4) from various sources, including a systematic search of Embase, MEDLINE, and Ovid Global Health, for literature published between Jan 1, 2000, and Dec 31, 2024; unpublished data contributed by an established collaborative network; and public viral surveillance datasets from online platforms. We included studies that continuously tested hPIVs throughout their study period and reported seasonal activity in defined geographical locations on a monthly basis (or if monthly data could be derived from reports). We excluded published studies if they had fewer than 20 cases, focused on specific medical conditions, or contained duplicate data from published literature or publicly available datasets. A prespecified collection template was used to collect data from members in the collaborative network. We extracted site-specific monthly case counts of combined hPIVs and each viral type and used the annual average percentage approach to assess relative circulating strength, epidemic onset and peak month, and epidemic duration by virus type and latitude. We identified type-specific transmission zones of countries with similar circulating patterns with the k-means method. A local regression model (selected by leave-one-out cross-validation) was used to explore climatic factors associated with variations in hPIV monthly circulating activity. The study was registered with PROSPERO, CRD42023370261. FINDINGS:We included 115 records in total: 103 studies identified from the published literature, five studies contributed by collaborators, and data from seven public surveillance datasets. We included 306 719 cases from 141 sites in 64 countries. We found that hPIV-3 exhibited distinctive seasonal patterns compared with the other three hPIV types. In temperate regions, hPIV-3 seasons typically occurred in spring, summer, and winter, with a median onset in April (IQR April-May) in the northern temperate region and July (July-July) in the southern temperate region. hPIV-1, hPIV-2, and hPIV-4 seasons typically occurred in autumn, winter, and summer, with median onsets between August and October in the northern temperate region and between April and May in the southern temperate region. Both epidemic onset and peak timing for hPIV-1, hPIV-2, and hPIV-4 were less consistent in tropical and subtropical regions than in temperate regions, whereas the seasonality of hPIV-3 remained generally consistent across regions. Northern temperate and subtropical countries typically clustered in shared transmission zones for hPIV-1, hPIV-2, and hPIV-3 with a few exceptions, as did countries in the southern hemisphere. Nevertheless, hPIV-1 and hPIV-4 peak timings were delayed as latitude increased in the northern hemisphere (Pearson's r=0·62 [p=0·0012] for hPIV-1 and r=0·53 [p=0·049] for hPIV-4). Type-specific climate models yielded better fits (with greater area under the receiver operating characteristic curve values) than models for combined hPIVs. In temperate regions, higher hPIV-1, hPIV-2, and hPIV-4 activity correlated with declining temperature and increasing relative humidity (all p values <0·0001), whereas higher hPIV-3 activity was correlated with rising temperature (rs=0·61; p<0·0001). In subtropical and tropical regions, the climate models showed suboptimal performance. Exploratory analyses showed differential timing shifts in hPIV epidemics across six included countries following the lifting of COVID-19 non-pharmacological interventions. INTERPRETATION:Our results characterise both between-type and regional variations in hPIV seasonality and the differential effects of monthly temperature variability and relative humidity on the global seasonality of different hPIV types. These findings have important implications for development of global hPIV surveillance and epidemic prediction in diverse locations. Substantial gaps in hPIV type-specific seasonality data remain in many countries, highlighting the need to expand surveillance to improve characterisation and prediction of hPIV epidemics. FUNDING:National Natural Science Foundation of China.
The interaction of nucleic acids (calf thymus DNA and pCY B3 plasmid, yeast RNA) with ethylenediamine Pd(II) and Pt(II) complexes containing aromatic heterocyclic ligands (2,2′-bipyridyl, 1,10-phenanthroline, 2-phenylpyridine, 2-(2′-thienyl)pyridine, 7,8-benzoquinoline, methyl 2-phenyl-4-quinolinecarboxylate, coumarin 6, and Nile red) has been studied using electron absorption spectroscopy and gel electrophoresis. The applicability of electron absorption spectroscopy for establishing the intercalation of organometallic complexes into DNA is demonstrated. Among the complexes under study, only Pd(II) complexes with Nile red and coumarin-6 are capable of intense interaction with RNA. Effective relaxing of supercoiled plasmid DNA, which is revealed by gel electrophoresis, indicates that the same complexes intercalate into DNA more actively than the other ones.