BACKGROUND:The role of human rhinovirus (HRV) in adult lower respiratory tract infections (LRTIs) remains controversial due to limited direct evidence of alveolar tropism and age-specific clinical characterization. OBJECTIVES:To determine HRV's clinical impact, validate its capacity to infect lower respiratory tract cells, and identify predictors for HRV-associated pneumonia in adults. METHODS:In this retrospective study (January 2020-December 2023), all hospitalized adults screened for HRV via RT-PCR were enrolled for analysis. In bronchoalveolar lavage fluid (BALF)-HRV-RNA-positive patients with available transbronchial lung biopsy (TBLB) or transbronchial cryobiopsy (TBCB) specimens, immunofluorescence (IF) staining was used to assess infection of LRT cells. Multivariable logistic regression analyzed demographics, comorbidities, and symptoms. RESULTS:HRV was detected in 4.6% (437/9544) of patients, with bimodal seasonal peaks (February-April and September-November). Co-infection occurred in 49.0% (214/437), predominantly bacteria (34.1%) and viruses (25.7%). Among the 437 HRV-positive patients, 224 cases complicated with pneumonia, but only 34 (7.8%) met the diagnostic criteria for simple viral pneumonia. Multivariate analysis identified male (OR 2.69, 95% CI 1.04-6.99, P = .042), fever (OR 3.79, 95% CI 1.52-9.44, P = .004), and cough (OR 7.33, 95% CI 1.64-32.83, P = .009) as independent predictors of simple rhinovirus pneumonia. IF staining confirmed HRV VP3 protein in TBLB/TBCB specimens in 61.5% (8/13) of cases, resolving debates about HRV's LRT cells tropism. CONCLUSIONS:This study provides the first histological evidence of HRV's LRT cells infection in immunocompetent adults. Despite high co-infection rates, HRV independently drives pneumonia, particularly in males and those with fever or cough.

The prevalence, epidemiological history and disease risk posed by pathogenic tick-borne viruses (TBVs) remain poorly understood in Northeast Asia. Here, over 12,000 ticks were collected from diverse ecological environments in Northeast China, leading to the identification of 44 TBVs from which 1,221 viral sequences were assembled. This included six human/mammal-infecting TBVs: Alongshan virus, Beiji nairovirus, Mukawa virus, Nuomin virus, tick-borne encephalitis virus (TBEV), and Yezo virus. Aga, Izumo, and Nishinomiya in Japan were identified as tick diversity hotspots, while Shangzhi City, Genhe City, and Raohe County in China were classified as TBV hotspots. We then performed an ecological modelling of seven human-infecting TBVs and their major tick species. Both TBVs and their tick vectors were projected to have a wider distribution potential than previously recognized, including the human-infecting Wetland virus (WELV) identified in 2024. Notably, aside from WELV, the other six human-infecting TBVs were predicted to circulate in all five Northeast Asian countries. Specifically, severe fever with thrombocytopenia syndrome virus was projected to potentially impact 266.74 million people, including nearly 100% of the population of Liaoning of China, the Republic of Korea (ROK) and the Democratic People's Republic of Korea (DPRK), and 91.6% of the Japanese population. TBEV was modelled to have the widest distribution potential area of 8.56 million km2 (95.4%), potentially impacting 226.65 million people (71.1%). Overall, our study highlighted Northeast China and its adjacent countries as high-risk regions for several human-infecting TBVs. It is imperative to prioritize preventive and therapeutic measures for these high-risk TBVs.

The role of farmed animals in the viral spillover from wild animals to humans is of growing importance. Between July and September of 2023 infectious disease outbreaks were reported on six Arctic fox (Vulpes lagopus) farms in Shandong and Liaoning provinces, China, which lasted for 2-3 months and resulted in tens to hundreds of fatalities per farm. Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) was identified in tissue/organ and swab samples from all the 13 foxes collected from these farms. These animals exhibited loss of appetite and weight loss, finally resulting in death. In autopsy and histopathology, prominently enlarged spleens and extensive multi-organ hemorrhage were observed, respectively, indicating severe systemic effects. Viral loads were detected in various tissues/organs, including brains from 9 of the 10 foxes. SFTSV was also detected in serum, anal swabs, as well as in environmental samples, including residual food in troughs used by dying foxes in follow-up studies at two farms. The 13 newly sequenced SFTSV genomes shared >99.43% nucleotide identity with human strains from China. Phylogenetic analyses showed that the 13 sequences belonged to three genotypes, and that two sequences from Liaoning were genomic reassortants, indicative of multiple sources and introduction events. This study provides the first evidence of SFTSV infection, multi-tissue tropism, and pathogenicity in farmed foxes, representing an expanded virus host range. However, the widespread circulation of different genotypes of SFTSV in farmed animals from different provinces and the diverse transmission routes, highlight its increasing and noticeable public health risk in China.

The prevalence, evolution, and disease risk of pathogenic tick-borne viruses (TBVs) remains poorly understood in northwest China and adjacent countries, which are endemic for several TBVs of public health importance. Herein, we perform meta-transcriptomic sequencing of >9600 ticks collected across this vast geographic area to identify 92 RNA viruses and assemble 1567 viral genomes from 28 different tick species, including ten human- and mammal-infecting TBVs. Tacheng tick virus 1 (TcTV-1), Tacheng tick virus 2 (TcTV-2), Tamdy virus (TAMV), and Crimean-Congo hemorrhagic fever virus (CCHFV) are the most common human-infecting TBVs detected. We also report several pathogenic TBVs not previously identified in China (Burana virus and Bhanja virus), Kazakhstan (TcTV-1), and northwest China (Wad Medani virus and Alongshan virus). We predict a significant increase in the number of high-risk regions for the four major tick vectors of pathogenic TBVs, and the distribution of TAMV, TcTV-1, TcTV-2, and CCHFV, with 65.4% of the counties in this region identified as high risk for CCHFV. Therefore, the real disease burden caused by TBVs in northwest China and adjacent countries may be more underestimated than appreciated, and we call for strengthened field surveys and epidemiological surveillance in this vast region.

Geckos are generally small, predominantly nocturnal reptiles, with several species commonly found close to human habitations. However, little is known about viral diversity in geckos. Using meta-transcriptomic sequencing we identified four novel RNA viruses - provisionally denoted Gecko astrovirus, Gecko parechovirus, Gecko reptillovirus, and Gecko hartmanivirus - in geckos sampled in October 2019 from Hainan Province, China. The presence of these viruses was confirmed by reverse transcription (RT)-PCR. Phylogenetic analyses revealed that these viruses were most closely related to those identified in various gecko species from China and Australia, such that they represent gecko-specific lineages, yet were also genetically distinct, with amino acid sequence identities to their closest relatives ranging from 38.6 % to 74.2 %. A co-phylogeny analysis revealed a complex interplay between long-term virus-host co-divergence and more recent host jumping, which differed in frequency among groups. In sum, we demonstrate the presence of four novel gecko-associated RNA viruses, expanding our understanding of viral diversity in these common animal species.

Tamdy virus (TAMV) is one of the zoonotic tick-borne bunyaviruses that have emerged as global public health threats in recent decades. To date, however, TAMV pathogenesis remains poorly understood. In the present study, we have established different mouse infection models to enable investigation of TAMV pathogenesis. Adult BALB/c mice did not exhibit obvious clinical symptoms or signs post-TAMV infection. In contrast, adult type I interferon receptor knockout (IFNAR-/-) A129 mice were found to be susceptible to high-doses of TAMV (6 × 102 and 6 × 104 FFU) and all developed severe clinical symptoms and signs, including weight loss and immobility, and reached the euthanasia criteria at 4/5-day post-infection (dpi). Viral RNA was detected in peripheral blood and different tissues (heart, liver, spleen, lung, kidney, intestine, and brain) of the high-dose infected adult A129 mice, with the highest viral loads in the liver (approximately 108.3 copies/μL). Pathological examination also revealed severe liver damage in the high-dose infected A129 mice. In addition, the titres of TAMV-specific IgM and IgG antibodies increased rapidly 4-5 dpi. Analysis of cytokine and chemokine expression changes demonstrated that type I IFN may play an important role in the host defence against viral infection by enhancing IL-10 production. Gene ontology and KEGG analyses showed that liver injury may be associated with virus-induced expression of inflammatory cytokines and chemokines. Together, we have investigated TAMV pathogenesis using immunocompetent and immunocompromised mouse models, which will facilitate the development of TAMV-specific antivirals and vaccines.

Human enteroviruses (EVs) represent a global public health concern due to their association with a range of serious pediatric illnesses. Despite the high morbidity and mortality exerted by EVs, no broad-spectrum antivirals are currently available. Herein, we presented evidence that doxycycline can inhibit in vitro replication of various neurotropic EVs, including enterovirus A71 (EV-A71), enterovirus D68 (EV-D68), and coxsackievirus (CV)-A6, in a dose-dependent manner. Further investigations indicated that the drug primarily acted at the post-entry stage of virus infection in vitro, with inhibitory effects reaching up to 89 % for EV-A71 when administered two hours post-infection. These findings provide valuable insights for the development of antiviral drugs against EV infections.

The Chinese tree shrew ( Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.

Venom is known as the source of natural antimicrobial products. Previous studies have largely focused on the expression of venom-related genes and the biochemical components of venom. With the advent of metagenomic sequencing, many more microorganisms, especially viruses, have been identified in highly diverse environments. Herein, we investigated the RNA virome in the venom-related microenvironment through analysis of a large volume of venom-related RNA-sequencing data mined from public databases. From this, we identified viral sequences belonging to thirty-six different viruses, of which twenty-two were classified as 'novel' as they exhibited less than 90 per cent amino acid identity to known viruses in the RNA-dependent RNA polymerase. Most of these novel viruses possessed genome structures similar to their closest relatives, with specific alterations in some cases. Phylogenetic analyses revealed that these viruses belonged to at least twenty-two viral families or unclassified groups, some of which were highly divergent from known taxa. Although further analysis failed to find venom-specific viruses, some viruses seemingly had much higher abundance in the venom-related microenvironment than in other tissues. In sum, our study provides insights into the RNA virome of the venom-related microenvironment from diverse animal phyla.

Nairobi Sheep Disease (NSD) is a typical tick-borne syndrome characterized by severe hemorrhagic gastroenteritis, spontaneous abortion, and a high case fatality rate in small ruminants. The pathogenic agent, Nairobi sheep disease virus (NSDV), has also been associated with human infections, indicating its possible zoonotic potential. Prior to this study, NSDV has been detected from ticks collected in Jilin, Hubei, and Liaoning provinces in China. In the present study, a total of 343 ticks (Haemaphysalis longicornis) were collected in Shandong province, China in 2020, and pooled into 16 libraries. Analysis of the meta-transcriptomic sequencing data identified NSDV strains SDWL07, SDWL08, and SDWL16 from three pools. The SDWL07 and SDWL16 strains were detected from unfed ticks, while SDWL08 was detected from cattle-feeding ticks. Phylogenetic analyses showed higher sequence identities between the three strains and other Chinese NSDV strains than those from India and Kenya. Phylogenetic analyses also revealed that they clustered together and fell within the China lineage, suggesting no potential genetic reassortment among them. In summary, this is the first report of the identification of NSDV in Shandong province, highlighting the continually expanding endemic regions of this pathogen. Surveillance of NSDV should be intensified in China, especially in areas where H. longicornis is endemic.

Hepeviruses have been identified in a broad range of animal hosts, including mammals, birds, and fish. In this study, rodents (n=91) from seven different species and ten pikas (Ochotona curzoniae) were collected in Qinghai Province, China. Using transcriptomic sequencing and confirmatory molecular testing, hepeviruses were detected in 27 of 45 (60 %) long-tailed dwarf hamsters (Cricetulus longicaudatus) and were undetected in other rodents and pika. The complete genome sequences from 14 representative strains were subsequently obtained, and phylogenetic analyses suggested that they represent a novel species within the genus Rocahepevirus, which we tentatively designated as Cl-2018QH. The virus was successfully isolated in human hepatoma (Huh-7) and murine fibroblast (17 Cl-1) cell lines, though both exhibited limited replication as assayed by detection of negative-sense RNA intermediates. A129 immunodeficient mice were inoculated with Cl-2018QH and the virus was consistently detected in multiple organs, despite relatively low viral loads. In summary, this study has described a novel rodent hepevirus, which enhances our knowledge of the genetic diversity of rodent hepeviruses and highlights its potential for cross-species transmission.

We isolated severe fever with thrombocytopenia syndrome virus (SFTSV) from farmed minks in China, providing evidence of natural SFTSV infection in farmed minks. Our findings support the potential role of farmed minks in maintaining SFTSV and are helpful for the development of public health interventions to reduce human infection.

This study revealed the huge capability of mosquitoes in harboring a rich diversity of RNA viruses, although relevant studies have characterized the intensively unparalleled diversity of RNA viruses previously. Furthermore, our findings showed discernible differences not only in viromic structure between mosquito genera and even between mosquito species within the same genus but also in the genetic diversity and abundance of Wolbachia between different mosquito populations.

The impairment of antibody-mediated immunity is a major factor associated with fatal cases of severe fever with thrombocytopenia syndrome (SFTS). By collating the clinical diagnosis reports of 30 SFTS cases, we discovered the overprolifera-tion of monoclonal plasma cells (MCP cells, CD38+cLambda+cKappa-) in bone marrow, which has only been reported previously in multiple myeloma. The ratio of CD38+cLambda+ versus CD38+cKappa+ in SFTS cases with MCP cells was significantly higher than that in normal cases. MCP cells presented transient expression in the bone marrow, which was distinctly different from multiple myeloma. Moreover, the SFTS patients with MCP cells had higher clinical severity. Further, the overproliferation of MCP cells was also observed in SFTS virus (SFTSV)-infected mice with lethal infectious doses. Together, SFTSV infec-tion induces transient overproliferation of monoclonal lambda-type plasma cells, which have important implications for the study of SFTSV pathogenesis, prog-nosis, and the rational development of therapeutics.

The economic and environmental value of honeybees has been severely challenged in recent years by the collapse of their colonies worldwide, often caused by outbreaks of infectious diseases. However, our understanding of the diversity, prevalence, and transmission of honeybee viruses is largely obscure due to a lack of large-scale and longitudinal genomic surveillance on a global scale. We report the meta-transcriptomic sequencing of nearly 2000 samples of the two most important economic and widely maintained honeybee species, as well as an associated ectoparasite mite, collected across China during 2016–2019. We document the natural diversity and evolution of honeybee viruses in China, providing evidence that multiple viruses commonly co-circulate within individual bee colonies. We also expanded the genomic data for 12 important honeybee viruses and revealed novel genetic variants and lineages associated with China. We identified more than 23 novel viruses from the honeybee and mite viromes, with some exhibiting ongoing replication in their respective hosts. Together, these data provide additional support to the idea that mites are an important reservoir and spill-over host for honeybee viruses. Our data show that honeybee viruses are more widespread, prevalent, and genetically diverse than previously realized. The information provided is important in mitigating viral infectious diseases in honeybees, in turn helping to maintain sustainable productive agriculture on a global scale.

Influenza C virus (ICV) was identified in five pediatric acute respiratory cases in Shandong. Co-infection with other respiratory viruses was detected in four of these cases. Two ICV genomes were obtained and clustered in the S1-sublineage of C/Sao Paulo/378/82, indicating that genetically diverse ICV strains have been circulating in mainland China.

Influenza C virus (ICV) was identified in five pediatric acute respiratory cases in Shandong. Co-infection with other respiratory viruses was detected in four of these cases. Two ICV genomes were obtained and clustered in the S1-sublineage of C/Sao Paulo/378/82, indicating that genetically diverse ICV strains have been circulating in mainland China.

lthough numerous tick-borne viruses are seemingly apathogenic in humans, a number of emerging tick-borne viruses have been recently identified to possess human-infection potential, with more yet to be discovered. Here, we call for greater research efforts to better delineate their precise disease burden and threats posed to global public health.