Shixing Yang

Microviricetes are small circular single-stranded DNA bacteriophages found in diverse environments, but their diversity in masked palm civet fecal viromes remains poorly characterized. Here, viral metagenomic analysis of five pooled fecal libraries from captive masked palm civets (Paguma larvata) recovered 14 high-quality Microviricetes genome candidates. Genome lengths ranged from 4996 to 6337 nt, with GC contents of 37.4–49.3%, and all genomes encoded homologues of VP1, VP2, and VP4. CheckV estimated completeness at 95.22–100.00% and classified all candidates as high-quality genomes. Comparative analysis identified five genome-organization patterns, while VP1 phylogeny placed the genomes within Gokushovirales and Alpavirales. Four of 24 additional VP1-containing contigs clustered with Betagokushoviridae references. VIRIDIC comparisons with 43 reference sequences showed that 13 genomes had maximum intergenomic similarities below the 80% species threshold, including eight below the 50% genus threshold. L13_863 shared 80.15% similarity with an unassigned reference genome but remained below 50% similarity to the included ICTV representatives. These findings support the presence of putative novel species and candidate novel genera and expand the known genomic diversity of Microviricetes associated with captive masked palm civet feces.

Metagenomic studies on the fecal virome of snow leopards, rare apex predators on the Qinghai-Tibet Plateau (QTP), remain limited. In this study, we utilized metagenomic sequencing to characterize the fecal viral community in captive QTP snow leopards. We assembled 22 complete viral genomes across the families Anelloviridae, Circoviridae, Parvoviridae, Picornaviridae, Genomoviridae, and Smacoviridae. Phylogenetic analyses indicated substantial sequence novelty. We identified 9 anellovirus genomes in the genera Tettorquevirus and Etatorquevirus , 3 candidate novel parvoviruses in Bocaparvovirus , Chaphamaparvovirus , and Dependoparvovirus , 3 circovirus genomes representing 2 candidate novel species, and 1 candidate novel sakobuvirus species. Another kobuvirus genome represented a divergent strain of a known species. In addition, 4 divergent genomoviruses showed phylogenetic relationships with sequences reported from diverse animal and environmental sources. Notably, one candidate novel porprismacovirus (family Smacoviridae) displayed a marked discordance between its highly conserved replication-associated protein (96.7% amino acid identity), divergent capsid protein (maximum identity, 59.7%), and low whole-genome identity (63.6%). Recombination analysis suggested it might be a recombinant virus. In summary, this study expands current knowledge of the diversity and evolutionary characteristics of viruses detected in snow leopard fecal samples and provides baseline genomic data for future investigation of captive snow leopard viromes.

In this study, viral metagenomic approach was employed to identify a novel canine papillomavirus (CPV) strain in the lymphoid tissue of a stray dog. The complete circular genome (8,297 bp) of a novel papillomavirus strain, designated canpapil01, was characterized and taxonomically assigned to the genus Taupapillomavirus. The genome encodes five early genes (E1, E2, E4, E6, E7) and two late genes (L1 and L2), lacking the E5 gene. Conserved motifs essential for viral replication and host interaction were identified, including ATP-binding and cyclin interaction sites in E1, DNA-binding domains in E2, and zinc-binding domains in E6 and E7. Notably, the pRb-binding motif (LXCXE) was absent in E7. The long control region (LCR) contained predicted E1 and E2-binding sites, indicating regulatory functions. Phylogenetic analysis based on the L1 gene revealed that canpapil01 clustered with Taupapillomavirus 2 strains, which were isolated from nasal swab or blood samples of dogs and wolves in the Switzerland and the USA, forming a separate branch. Genome-wide comparisons showed 71.4% amino acid identity with the Taupapillomavirus 2 reference strain (NC_040578), confirming it as a novel strain within this species. These findings expand the known genetic diversity of canine papillomaviruses and provide valuable genomic data for future research into CPV-associated diseases.

Tripartite motif-containing protein 21 (TRIM21/Ro52) is a pivotal E3 ubiquitin ligase and cytoplasmic fragment crystallizable receptor (FcR). It plays a crucial role in viral infections, autoimmune disorders, and cancers by regulating multiple cell signaling axes, including the NF-κB, RIG-I-like receptor (RLR), cGAS-STING, and Toll-like receptor (TLR) pathways. Type I interferon (IFN-I), a pleiotropic cytokine, is produced via these immune signaling pathways, which are often triggered by viral components. TRIM21 both activates IFN-I signaling and mediates its negative feedback through post-translational modification of key immune signaling proteins, thereby maintaining immune homeostasis. In recent years, TRIM21 has been found to dually regulate autophagy and IFN-I in the context of virus–host interplay. Herein, we systematically summarize the functional roles of TRIM21 in virus-triggered intracellular immunity, aiming to provide insights for researchers and inspire further investigation in this area.

Respiratory tract infections represent a leading cause of morbidity and mortality globally, with viral pathogens accounting for a substantial proportion of these cases. However, research on the human respiratory virome is still in its infancy, and our understanding of this field remains relatively limited. In the present study, viral metagenomic sequencing was conducted on 65 sputum samples obtained from patients with severe fungal infections. We successfully assembled viral genome sequences belonging to four distinct viral families: Anelloviridae, Genomoviridae, Microviridae, and Inoviridae . Through systematic analysis of the virome composition, this study characterized the structural features of the respiratory virome in patients with severe fungal infections. The findings provide a foundational description of viral diversity in this specific clinical context. These findings lay a theoretical foundation for clinical pathogen detection, targeted interventions, and the development of future prevention strategies.

Human endogenous retroviruses (HERVs), constituting roughly 8% of the human genome, have undergone a profound conceptual evolution from dismissed genomic “fossils” to critical, dualistic regulators in cancer biology. Their pathognomonic reactivation across malignancies orchestrates tumorigenesis through three interconnected molecular axes: (1) genomic destabilization via LTR-mediated insertional mutagenesis, disrupting key loci such as TP53 and MYC ; (2) immune checkpoint subversion, driven by HERV-K envelope glycoprotein-induced PD-L1 upregulation (2.3-fold; p < 0.01); and (3) chronic inflammatory signaling triggered by double-stranded RNA (dsRNA) activation of innate immune pathways (TLR3/MDA5/NLRP3). This foundational mechanistic insight is accelerating clinical translation. Diagnostic advances now feature HERV-K Env-targeted liquid biopsies achieving 92% specificity (AUC = 0.94) for early-stage tumors and artificial intelligence (AI)-enhanced platforms (e.g., DeepHERV, AUC = 0.91) that resolve complex HERV expression landscapes. Therapeutically, an emerging pipeline of strategies is rapidly advancing, from initial first-in-human clinical trials (NCT05687903, NCT05554866) of HERV-directed monoclonal antibodies and vaccines to the highly promising preclinical efficacy demonstrated by HERV-K-specific chimeric antigen receptor (CAR) T-cells (> 70% tumor regression) and locus-precise CRISPR/Cas9 epigenetic silencing. However, clinical translation is complicated by persistent challenges, including intratumoral HERV heterogeneity, a lack of assay standardization (as evidenced by 60% primer discordance), and the fundamental ethical and therapeutic requirement for specificity—that is, precise discrimination between pathogenic HERVs and their essential physiological counterparts. A convergent translational framework—leveraging international consortia for biomarker validation, machine learning for patient stratification, and engineered tumor-selective delivery platforms—is now positioned to harness this novel target class and redefine the next era of precision oncology.

Introduction: The Great Cormorant (Phalacrocorax carbo) is widely distributed across China. As an apex predator in aquatic ecosystems, it plays a tripartite ecological role: acting as a natural host, transmission vector, and indicator species for viruses. Current research confirms that cormorants carry diverse viral pathogens from the families including Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Polyomaviridae. Significant knowledge gaps persist regarding their virome diversity.Methods: In this study,46 cormorant fecal swab samples were collected at Xiamen Garden Expo Park, and viralmetagenomics method was conducted to identify two Cycloviruses.Results: This study identified two novel cycloviruses, Corcyclo-1 (1,856 bp) and Corcyclo-2 (1,831 bp), from cormorant fecal samples using viral metagenomics. Genomic analyses revealed hallmark features of the genus Cyclovirus, including inversely oriented open reading frames (ORFs) encoding the capsid protein (Cap) and replication-associated protein (Rep), as well as a conserved stem-loop sequence TAATACTAT. The Rep gene of Corcyclo-1 contained a 166-bp intron and shared >96.9% amino acid identity with human-, wild boar-, and chicken-derived cyclovirus strains (HaCV-8) from Vietnam and Madagascar, classifying it as a novel strain of HaCV-8. In contrast, Corcyclo-2 harbored a 98-bp intron in its Rep gene and clustered with unclassified cyclovirus strains from bats and mongooses in China and Saint Kitts and Nevis (>97.4% identity), constituting a putative new species. Phylogenetic and pairwise sequence analyses further supported their taxonomic positions. Epidemiological screening demonstrated a high prevalence of Corcyclo-1 (82.6%, 38/46) and Corcyclo-2 (32.6%, 15/46) in cormorant feces. Cross-species surveillance detected Corcyclo-2 in chickens (25.8%, 16/62) and ducks (11.7%, 9/77), whereas Corcyclo-1 was absent in these hosts.Conclusion: This study represents the first report of cormorant-associated cycloviruses, highlighting their potential for cross-species transmission and providing new insights into the ecological diversity and evolutionary mechanisms of cyclovirus.

Introduction: Cormorants, as protected wild animals by the State Forestry Administration of China, have a broad distribution across China. Previous studies have shown that they can be infected with multiple viruses in the Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Polyomaviridae families. There is limited knowledge about the other viruses that cormorants may carry and infect.Methods: In this study, we employed viral metagenomics to identify novel viruses in the fecal samples collected from cormorants in Xiamen City, Fujian Province, China.Results: Two novel viruses were identified, including one novel picornavirus named Cormhepa01 and one novel avain hepevirus named CormhepaE. The genome of Cormhepa01 is 7,463 bp in length, which encodes a 2,260 aa polyprotien. Similar to other known picornaviruses, the conserved NTPase, proteinase, and polymerase motifs are presented in the 2C, 3C, and 3D proteins separately. Based on the phylogenetic analysis and amino acid sequence alignment, the CormhepaE may be assigned to a new picornavirus genus. The partial genome of CormhepaE is 6,546 bp in length. Compared with other avian hepatitis E virus strains, CormhepaE has multiple variable sites, which are distributed in motifs of the methyltransferase, helicase, and RdRp domains, separately. Based on the phylogenetic analysis, CormhepaE, together with another strain MG737712 isolated from sparrow, formed a new species of the Avihepevirus genus in the Hepeviridae family.Conclusion: We identified and characterized two novel cormorant viruses in this study. The findings of this study increase our understanding of the diversity of viruses in cormorants and provide practical viral genome information for the prevention and treatment of potential viral diseases affecting this species.