Orthobunyavirus refers to the virus members within the Genus Orthobunyavirus, which is the largest virus genus in the Family Peribunyaviridae and even Class Bunyaviricetes. To date, over 130 species of Orthobunyaviruses have been identified worldwide. Orthobunyaviruses mainly infect arthropods, while some species are capable of being transmitted to mammals, including humans, via intermediate vectors. As emerging and re-emerging pathogens, orthobunyavirus poses a significant threat to both human and veterinary public health worldwide. Currently, there are no commercial vaccines against orthobunyavirus. The structure of orthobunyavirus is relatively simple, consisting of a typical tri-segmented negative-sense RNA genome that encodes four structural proteins (L, Gn, Gc, and N) and two non-structural proteins (NSm and NSs). The highly glycosylated Gc protein, which has a complex conformation and forms polymers embedded in the viral envelope, plays a critical role in inducing neutralizing antibodies throughout the orthobunyavirus infection cycle from entry to egress. This review provides a comprehensive summary of the virus-encoded Gc protein and its role in the virus life cycle from viral entry to egress, offering researchers with valuable integrated information for further investigations.

The Porcine reproductive and respiratory syndrome virus (PRRSV), a single (+) RNA virus, is characterized by high genome variability and constant evolution. Owing to increasingly complex mutations, there is a growing difficulty in accessing the whole genome. Additionally, there is limited knowledge on PRRSV intra-host nucleotide variants, which may reflect the complex viral-host dynamics. Here, we performed next-generation sequencing on four clinical lung tissues to reveal the genomic diversity and highlight virus-host interactions. The complete genomes of the HN0713 and GDYJ1224 strains shared 90.7% and 91.3% homology with the lineage 1 strain NADC30, respectively, while the GDGZ0408 and GDHY0425 strains shared 92.0% and 91.6% homology with the JXA1 strain, respectively. Recombination analysis showed that the ORF5-7 genes of the GDGZ0408 and GDHY0425 strains, whose complete genomes belong to lineage 8.7 based on the phylogenetic tree, are both recombined with lineage 3 strains. Furthermore, nsp3, nsp10-12, ORF2 genes and a part of the 3 '-UTR of the GDHY0425 strain were provided by the lineage 5.1 strain. Two lineage 1 strains (GDYJ1224 and HN0713) were produced by a recombination of lineages 8.7 and 1. Additionally, the lineage 3 strain was associated with the recombinant HN0713 strain. We determined the intra-host single nucleotide variant frequencies and found more than 200 sites at a frequency of >1% in all samples. GDGZ0408 with parts of the nsp9 and nsp10 genes of HP-PRRSV lineage 8.7 presented more genetically diverse populations than others, indicating that lineage 8.7 might drive robust intra-host single nucleotide variants (iSNVs). Moreover, in the iSNV pools, nsp2 and ORF2a presented the highest mutation dynamic. Overall, this study provided evidence for the alarmingly increasing recombination and ever-changing evolutionary dynamics of PRRSV, and revealed the potential causes of vaccine escape, providing a novel insight into the nucleotide variant population in clinical samples.

Orthobunyaviruses, including La Crosse virus (LACV), Oropouche virus (OROV), Schmallenberg virus (SBV), and Akabane virus (AKAV), pose substantial threats to global public health and livestock industries. This review focuses on the interplay between these viruses and the host immune systems, highlighting key mechanisms of viral entry and immune evasion. The viruses exploit vulnerabilities in host innate immunity, particularly through nonstructural protein NSs, which disrupts type I interferon signaling and transcriptional machinery. Additionally, this review delineates how host restriction factors counteract viral proliferation through compartmentalized defense mechanisms including BST-2 and MxA. The review also discusses antiviral strategies, including vaccines and inhibitors. Hence, this review synthesizes current knowledge on host recognition, immune evasion, and therapies for Orthobunyaviruses infections (focusing on LACV, OROV, AKAV, SBV) to guide targeted antiviral and broad-spectrum countermeasure development against emerging Orthobunyaviruses threats.

Cats ( Felidae ) have become an integral part of many households. However, our understanding of the full spectrum of pathogens affecting cats (referred to as the infectome) is limited, mainly due to the inadequacy of commonly used diagnostic tools in capturing the complete diversity of potential pathogens and the prevalence of pathogen co-infections. In this study, we employed a meta-transcriptomic approach to simultaneously characterize the infectome contributing to different disease syndromes and to investigate spatial, demographic, and ecological factors influencing pathogen diversity and community composition in a cohort of 27 hospitalized cats and seven stray cats. We identified 15 species of pathogens, with Candidatus Rickettsia tarasevichiae and Tritrichomonas foetus representing potential spillover risks. Importantly, although most cases of ascites hyperplasia were explained by coinfection with multiple pathogens, we identified the potential novel clinical outcomes of M. aubagnense infection among cats. We demonstrated that the increase in infectome diversity can be explained by a variety of predictors including age growth, temperature increase, and a higher proportion of females, with age growth presenting the strongest effect. Fine-scale analysis indicated that a higher diversity of infectomes were harbored in young cats rather than adult ones. Our results demonstrated that most feline diseases are better explained by the presence of virus–bacteria or virus–virus coinfection. This study serves as a timely endorsement for clinical diagnosis by vets to consider the cause of a disease based on a panel of cryptical co-infecting pathogens rather than on individual infectious agents. IMPORTANCE: Frequent studies reported the risks of cats as an intermediate host of zoonotic pathogens (e.g., SARS-CoV-2). Cats have a physically close interaction with their owners through activities like petting, kissing, and being licked on the cheek and hands. However, there are still limited studies that systematically investigate the infectome structure of cats. In this study, we employed a meta-transcriptomics approach to characterize 15 species of pathogens in cats, with Candidatus Rickettsia tarasevichiae first characterizing infection in diseased cats. Most feline diseases were better explained by the presence of virus–bacteria or virus–virus coinfection. The increase in infectome diversity could be influenced by a variety of predictors including age growth, temperature increase, and a higher proportion of females. A higher diversity of pathogens was harbored in young cats rather than adults. Importantly, we showed the value of linking the modern influx of meta-transcriptomics with comparative ecology and demography and of utilizing it to affirm that ecological and demographic variations impact the total infectome.