Zhen Zhu

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017–2021, resulting in the acquisition of 112 HAdV strains. HAdV‐type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV‐3, 7, 55), species C (HAdV‐1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV‐4). Among these, HAdV‐3 exhibited the highest detection rate (44.6%), followed by HAdV‐7 (19.6%), HAdV‐1 (12.5%), and HAdV‐108 (9.8%). All HAdV‐3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV‐C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV‐1 and HAdV‐108 considered the two main types of HAdV‐C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV‐associated respiratory infections among hospitalized pediatric patients.

To determine the epidemiological status of influenza and understand the distribution of common respiratory viruses in adult patients with influenza-like illness (ILI) cases in Taiyuan City, Shanxi Province, China, epidemiological data between 2018 and 2019 were retrieved from the China Influenza Surveillance Information System, and two sentinel ILI surveillance hospitals were selected for sample collection. All specimens were screened for influenza virus (IFV) and the other 14 common respiratory viruses using real-time polymerase chain reaction. The results of the 2-year ILI surveillance showed that 26,205 (1.37%) of the 1,907,869 outpatients and emergency patients presented with ILI, with an average annual incidence of 297.75 per 100,000 individuals, and ILI cases were predominant in children <15 years (21,348 patients, 81.47%). Of the 2713 specimens collected from adult patients with ILI, the overall detection rate of respiratory viruses was 20.13%, with IFV being the most frequently detected (11.79%) and at a relatively lower rate than other respiratory viruses. Further subtype analysis indicated an alternating or mixed prevalence of H1N1 (2009), H3N2, Victoria, and Yamagata subtypes. This study provides a baseline epidemiological characterization of ILI and highlights the need for a nationwide detection and surveillance system for multiple respiratory pathogens.

HAdV types in cases of conjunctivitis in Shanxi province, China, in 2016 to 2019 showed evident diversity, with seven types (HAdV-3, HAdV-4, HAdV-8, HAdV-37, HAdV-53, HAdV-64, and HAdV-85) being identified, and relative genome stability of these viruses was observed. In addition, China was the second country to sample and isolate HAdV-85, which suggests that HAdV-85 might be underreported as an important pathogen associated with ocular infections.

To better understand the circulation pattern and genetic characterization of human respiratory syncytial virus (HRSV) in China during 2008–2021, a total of 3967 HVR2 sequences were obtained from 20 provinces in China for phylogenetic analysis and sequence variation analysis. The results showed that the HRSV subtype presented the prevalence pattern of “ABBAABAABAAABB.” Further genotyping identified seven genotypes for HRSVA and nine genotypes for HRSVB. Multiple genotypes of HRSV were cocirculating during 2008–2015, while ON1 and BA9 became the only predominant genotypes for HRSVA and HRSVB, respectively, since 2015. A genotype switch from NA1 to ON1 for HRSVA occurred in approximately 2014, while genotype BA9 of HRSVB had been the predominant genotype for at least 14 years. ON1 strains could be divided into four lineages with no temporal or geographical distribution tendency. In contrast, BA9 strains could be divided into three lineages with noticeable temporal clustering. Sequence variation analysis showed that two ON1 sequences in 2017 had 10 nucleotide deletion and compensatory extension at the C‐terminal; 15 BA9 sequences during 2019–2021 had novel insertions between K225 and E226, along with 6 identical amino acid variant sites. This study further enriched the genetic data of HRSV circulating in China and provided an important basis for the development of HRSV vaccines and drugs as well as the formulation of prevention and control strategies.

To better understand the importation and circulation patterns of rubella virus lineages 1E-L2 and 2B-L2c circulating in China since 2018, 3,312 viral strains collected from 27 out of 31 provinces in China between 2018 and 2021 were sequenced and analyzed with the representative international strains of lineages 1E-L2 and 2B-L2c based on genotyping region. Time-scale phylogenetic analysis revealed that the global lineages 1E-L2 and 2B-L2c presented distinct evolutionary patterns. Lineage 1E-L2 circulated in relatively limited geographical areas (mainly Asia) and showed geographical and temporal clustering, while lineage 2B-L2c strains circulated widely throughout the world and exhibited a complicated topology with several independently evolved branches. Furthermore, both lineages showed extensive international transmission activities, and phylogeographic inference provided evidence that lineage 1E-L2 strains circulating in China possibly originated from Japan, while the source of lineage 2B-L2c isolated since 2018 is still unclear. After importation into China in 2018, the spread of lineage 1E-L2 presented a three-stage transmission pattern from southern to northern China, whereas lineage 2B-L2c spread from a single point in western China to all the other four regions. These two transmission patterns allowed both imported lineages to spread rapidly across China during the 2018–9 rubella epidemic and eventually established endemic circulations. This study provides critical scientific data for rubella control and elimination in China and worldwide.

Measles is one of the most infectious diseases of humans. It is caused by the measles virus (MeV) and can lead to serious illness, lifelong complications, and even death. Whole‐genome sequencing (WGS) is now available to study molecular epidemiology and identify MeV transmission pathways. In the present study, WGS of 23 MeV strains of genotype H1, collected in Mainland China between 2006 and 2018, were generated and compared to 31 WGSs from the public domain to analyze genomic characteristics, evolutionary rates and date of emergence of H1 genotype. The noncoding region between M and F protein genes (M/F NCR) was the most variable region throughout the genome. Although the nucleotide substitution rate of H1 WGS was around 0.75 × 10⁻³ substitution per site per year, the M/F NCR had an evolutionary rate three times higher, with 2.44 × 10⁻³ substitution per site per year. Phylogenetic analysis identified three distinct genetic groups. The Time of the Most Recent Common Ancestor (TMRCA) of H1 genotype was estimated at approximately 1988, while the first genetic group appeared around 1995 followed by two other genetic groups in 1999–2002. Bayesian skyline plot showed that the genetic diversity of the H1 genotype remained stable even though the number of MeV cases decreased 50 times between 2014 (52 628) and 2020 (993). The current coronavirus disease 2019 (COVID‐19) pandemic might have some effect on the measles epidemic and further studies will be necessary to assess the genetic diversity of the H1 genotype in a post‐COVID area.

Background: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin‐dependent kinase 5 (CDK5) regulatory subunit‐associated protein 1‐like 1 (CDKAL1).Objective: To examine whether this polymorphism was involved in the susceptibility in first‐episode drug‐naive schizophrenic patients (FDSP), and further influenced their clinical symptoms.Methods: This polymorphism was genotyped in 239 FDSP and 368 healthy controls. The clinical symptoms in FDSP were assessed using the Positive and Negative Syndrome Scale (PANSS) five‐factor models.Results: There was no significant difference in the allelic and genotypic frequencies of this polymorphism between two groups (both p > 0.05) after adjusting for covariates. However, the PANSS depressive score significantly differed by genotype in FDSP after adjusting for covariates (F = 5.25, p = 0.006). This significant difference also persisted after Bonferroni correction (p < 0.05). FDSP with C/C genotype had significantly higher PANSS depressive score than those with C/G genotype (p = 0.007) and those with G/G genotype (p = 0.005). Moreover, further stepwise multivariate regression analysis showed the significant association between the rs7754840 polymorphism and PANSS depressive score in FDSP (β = −1.07, t = −2.75, p = 0.007).Conclusions: Our findings demonstrated that although the CDKAL1 rs7754840 polymorphism did not contribute to the susceptibility to FDSP, it might be implicated in depressive symptoms in this patient group.

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012–2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.