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PLoS Pathogens Feb 2024Human astrovirus (HAstV) is a known cause of viral gastroenteritis in children worldwide, but HAstV can cause also severe and systemic infections in immunocompromised...
Human astrovirus (HAstV) is a known cause of viral gastroenteritis in children worldwide, but HAstV can cause also severe and systemic infections in immunocompromised patients. There are three clades of HAstV: classical, MLB, and VA/HMO. While all three clades are found in gastrointestinal samples, HAstV-VA/HMO is the main clade associated with meningitis and encephalitis in immunocompromised patients. To understand how the HAstV-VA/HMO can infect the central nervous system, we investigated its sequence-divergent capsid spike, which functions in cell attachment and may influence viral tropism. Here we report the high-resolution crystal structures of the HAstV-VA1 capsid spike from strains isolated from patients with gastrointestinal and neuronal disease. The HAstV-VA1 spike forms a dimer and shares a core beta-barrel structure with other astrovirus capsid spikes but is otherwise strikingly different, suggesting that HAstV-VA1 may utilize a different cell receptor, and an infection competition assay supports this hypothesis. Furthermore, by mapping the capsid protease cleavage site onto the structure, the maturation and assembly of the HAstV-VA1 capsid is revealed. Finally, comparison of gastrointestinal and neuronal HAstV-VA1 sequences, structures, and antigenicity suggests that neuronal HAstV-VA1 strains may have acquired immune escape mutations. Overall, our studies on the HAstV-VA1 capsid spike lay a foundation to further investigate the biology of HAstV-VA/HMO and to develop vaccines and therapeutics targeting it.
Topics: Child; Humans; Capsid; Mamastrovirus; Capsid Proteins; Mutation; Astroviridae Infections; Phylogeny; Feces
PubMed: 38416796
DOI: 10.1371/journal.ppat.1012028 -
Poultry Science Apr 2024Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no...
Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no commercial veterinary products are available to prevent and treat the disease. Our previous studies showed that nitric oxide (NO) and inducible NO synthase (iNOS) were markedly higher in the kidney and spleen of goslings infected with GAstV-2, but their effects during GAstV-2 infection remain unclear. In the present study, goslings were intraperitoneally injected with aminoguanidine (AG)-an iNOS inhibitor-to examine the role of NO during GAstV-2 infection. AG significantly decreased the serum NO concentration and iNOS mRNA expression in the kidney. Moreover, AG reduced the mortality, serum uric acid and creatinine content, and urate deposition in visceral organs and joints. Histopathological analysis demonstrated that AG reduced renal tubular cell necrosis, inflammatory cell infiltration, glycogen deposition in glomerular mesangium, and interstitial fibrosis, suggesting alleviation of kidney lesions. Furthermore, AG decreased the expression of renal injury markers such as KIM-1 and desmin; inflammatory cytokine-related genes such as IL-1β, IL-8, and MMP-9; and autophagy-related genes and proteins such as LC3II, ATG5, and Beclin1. However, quantitative real-time PCR and immunohistochemistry showed that treatment with AG did not affect the kidney and liver viral load. These findings suggest that AG decreases the mortality rate and kidney lesions in goslings infected with GAstV-2 through mechanisms associated with autophagy and inhibition of inflammatory cytokine production in the kidney but not with GAstV-2 replication.
Topics: Animals; Geese; Uric Acid; Chickens; Astroviridae; Gout; Astroviridae Infections; Kidney; Cytokines; Avastrovirus; Guanidines
PubMed: 38306918
DOI: 10.1016/j.psj.2024.103484 -
Viral Immunology Apr 2024Goose astrovirus type 2 (GAstV-2) is a novel pathogen causing visceral gout in goslings; it not only causes necrosis of renal epithelial cells but also causes spleen...
Goose astrovirus type 2 (GAstV-2) is a novel pathogen causing visceral gout in goslings; it not only causes necrosis of renal epithelial cells but also causes spleen damage, indicating that GAstV-2 induces immunosuppression in goslings. However, to date, the interaction between GAstV-2 and immune cells remains unclear. In this study, peripheral blood lymphocytes and macrophages were isolated from goslings without GAstV-2 infection and then inoculated with GAstV-2, and the virus localization in the lymphocytes and macrophages, proliferation and apoptosis of lymphocytes, and phagocytic activity, reactive oxygen species (ROS) and nitric oxide (NO) production, and cell polarity in macrophages were determined. The results showed that GAstV-2 was observed in the cytoplasm of CD4 and CD8 T cells and macrophages, indicating that GAstV-2 can infect both lymphocytes and macrophages. GAstV-2 infection reduced the lymphocyte proliferation induced by Concanavalin A and lipopolysaccharide stimulation and increased the lymphocyte apoptosis rate and mRNA expression of Fas, demonstrating that GAstV-2 causes damage to lymphocytes. Moreover, GAstV-2 infection enhanced phagocytic activity and production of ROS and NO and induced a proinflammatory phenotype in macrophages (M1 macrophages), indicating that macrophages play an antiviral role during GAstV-2 infection. In conclusion, these results demonstrate that GAstV-2 infection causes damages to lymphocytes, and host macrophages inhibit GAstV-2 invasion during infection.
Topics: Animals; Humans; Geese; Reactive Oxygen Species; Lymphocytes; Macrophages; Astroviridae Infections; Nitric Oxide
PubMed: 38574260
DOI: 10.1089/vim.2023.0098 -
Food and Environmental Virology Apr 2024Viral metagenomics is a useful tool for detecting multiple human viruses in urban sewage. However, more refined protocols are required for its effective use in disease...
Viral metagenomics is a useful tool for detecting multiple human viruses in urban sewage. However, more refined protocols are required for its effective use in disease surveillance. In this study, we investigated the performance of three different preamplification pipelines (specific to RNA viruses, DNA viruses or both) for viral genome sequencing using spiked-in Phosphate Buffered Saline and sewage samples containing known concentrations of viruses. We found that compared to the pipeline targeting all genome types, the RNA pipeline performed better in detecting RNA viruses in both spiked and unspiked sewage samples, allowing the detection of various mammalian viruses including members from the Reoviridae, Picornaviridae, Astroviridae and Caliciviridae. However, the DNA-specific pipeline did not improve the detection of mammalian DNA viruses. We also measured viral recovery by quantitative reverse transcription polymerase chain reaction and assessed the impact of genetic background (non-viral genetic material) on viral coverage. Our results indicate that viral recoveries were generally lower in sewage (average of 11.0%) and higher in Phosphate Buffered Saline (average of 23.4%) for most viruses. Additionally, spiked-in viruses showed lower genome coverage in sewage, demonstrating the negative effect of genetic background on sequencing. Finally, correlation analysis revealed a relationship between virus concentration and genome normalized reads per million, indicating that viral metagenomic sequencing can be semiquantitative.
PubMed: 38647859
DOI: 10.1007/s12560-024-09594-3 -
Virology Oct 2023Little is known about the diversity of RNA viruses in geothermal systems. We generated total RNA sequencing data from two hot springs in Kuirau Park, Rotorua, New...
Little is known about the diversity of RNA viruses in geothermal systems. We generated total RNA sequencing data from two hot springs in Kuirau Park, Rotorua, New Zealand. In one data set, from a 71.8 °C pool, we observed a microbial community that was 98.5% archaea. The second data set, representing a cooler 36.8 °C geothermal hot spring, had a more diverse microbial profile: 58% bacteria, 34.5% eukaryotes and 7.5% archaea. Within this latter pool, we detected sequences likely representing 23 RNA viruses from the families Astroviridae, Tombusviridae, Polycipiviridae, Discistroviridae, Partitiviridae, and Mitoviridae, as well as from unclassified clades of the orders Tolivirales, Picornavirales, and Ghabrivirales. Most viruses had uncertain host associations. Of particular note, we identified four novel RNA viruses from the phylum Lenarviricota, commonly associated with bacteria and fungi, that occupied a divergent phylogenetic position within unclassified clades and may represent an ancient order-level taxon of unknown host association.
PubMed: 37647722
DOI: 10.1016/j.virol.2023.109873 -
BMC Genomics Jun 2024Virome studies on birds, including chickens are relatively scarce, particularly from the African continent. Despite the continuous evolution of RNA viruses and severe...
BACKGROUND
Virome studies on birds, including chickens are relatively scarce, particularly from the African continent. Despite the continuous evolution of RNA viruses and severe losses recorded in poultry from seasonal viral outbreaks, the information on RNA virome composition is even scantier as a result of their highly unstable nature, genetic diversity, and difficulties associated with characterization. Also, information on factors that may modulate the occurrence of some viruses in birds is limited, particularly for domesticated birds. Viral metagenomics through advancements in sequencing technologies, has enabled the characterization of the entire virome of diverse host species using various samples.
METHODS
The complex RNA viral constituents present in 27 faecal samples of asymptomatic chickens from a South African farm collected at 3-time points from two independent seasons were determined, and the impact of the chicken's age and collection season on viral abundance and diversity was further investigated. The study utilized the non-invasive faecal sampling method, mRNA viral targeted enrichment steps, a whole transcriptome amplification strategy, Illumina sequencing, and bioinformatics tools.
RESULTS
The results obtained revealed a total of 48 viral species spanning across 11 orders, 15 families and 21 genera. Viral RNA families such as Coronaviridae, Picornaviridae, Reoviridae, Astroviridae, Caliciviridae, Picorbirnaviridae and Retroviridae were abundant, among which picornaviruses, demonstrated a 100% prevalence across the three age groups (2, 4 and 7 weeks) and two seasons (summer and winter) of the 27 faecal samples investigated. A further probe into the extent of variation between the different chicken groups investigated indicated that viral diversity and abundance were significantly influenced by age (P = 0.01099) and season (P = 0.00099) between chicken groups, while there was no effect on viral shedding within samples in a group (alpha diversity) for age (P = 0.146) and season (P = 0.242).
CONCLUSION
The presence of an exceedingly varied chicken RNA virome, encompassing avian, mammalian, fungal, and dietary-associated viruses, underscores the complexities inherent in comprehending the causation, dynamics, and interspecies transmission of RNA viruses within the investigated chicken population. Hence, chickens, even in the absence of discernible symptoms, can harbour viruses that may exhibit opportunistic, commensal, or pathogenic characteristics.
Topics: Animals; Chickens; South Africa; Feces; Virome; Metagenomics; RNA, Viral; RNA Viruses; Farms; Metagenome; Seasons
PubMed: 38914944
DOI: 10.1186/s12864-024-10517-6 -
Infection, Genetics and Evolution :... Aug 2024Caliciviruses (Caliciviridae) and astroviruses (Astroviridae) are among the leading cause of non-bacterial foodborne disease and gastroenteritis in human. These...
Caliciviruses (Caliciviridae) and astroviruses (Astroviridae) are among the leading cause of non-bacterial foodborne disease and gastroenteritis in human. These non-enveloped RNA viruses infect a wide range of vertebrate species including rodents. Rodents are among the most important hosts of infectious diseases globally and are responsible for over 80 zoonotic pathogens that affect humans. Therefore, screening pathogens in rodents will be is necessary to prevent cross-species transmission to prevent zoonotic outbreaks. In the present study, we screened caliciviruses and astroviruses in order to describe their diversity and whether they harbor strains that can infect humans. RNA was then extracted from intestine samples of 245 rodents and retrotranscribed in cDNA to screen caliciviruses and astroviruses by PCRs. All the samples tested negative for caliciviruses and while astroviruses were detected in 18 (7.3%) samples of Rattus rattus species. Phylogenetic analyses based on the RdRp gene showed that all the sequences belonged to Mamastrovirus genus in which they were genetically related to R. rattus related AstVs previously detected in Gabon or in Rattus spp. AstV from Kenya and Asia. These findings suggested that transportation such as land and railway, as well national and international trade, are likely to facilitate spread of AstVs by the dissemination of rodents.
Topics: Animals; Phylogeny; Astroviridae; Caliciviridae Infections; Astroviridae Infections; Caliciviridae; Rodentia; Commerce; Rats; Humans
PubMed: 38806078
DOI: 10.1016/j.meegid.2024.105607 -
Brazilian Journal of Veterinary Medicine 2023The canine circovirus (CanCV) is a single-stranded DNA virus that has become an important emerging virus associated with gastroenteritis in dogs worldwide. In the...
The canine circovirus (CanCV) is a single-stranded DNA virus that has become an important emerging virus associated with gastroenteritis in dogs worldwide. In the present study, the CanCV was detected by PCR in 15% (22/147) of dogs from animal shelters in Belém, between 2019 and 2020. We observed an association between the CanCV infection and the presence of diarrhea in animals younger than one year of age (p > 0.01). The Brazilian strains were grouped in Chinese genotypes, with 99.54 to 100% nucleotilde homology. The GMRF Bayesian Skyride used the molecular clock model, which was the best suited technique to plot the dataset. The most recent common ancestor (TMRCA) was estimated in 2017, with the evolution rate of 1.6 x 10 s/s/y. The viral family diversity was also investigated, with emphasis on the families of the enteric pathogenic viruses Parvoviridae, Picornaviridae and Astroviridae, which were detected in the CanCV positive pooled samples. This study highlights the importance of the CanCV as an emergent virus that causes diarrhea in Brazilian dogs. The results found herein contribute to the understanding of the role of CanCV in enteric diseases and in the evolutionary molecular characterization of the circulating genotypes. Furthermore, we increased the understanding of the fecal virome in dogs with diarrhea, providing data for the monitoring and prevention viral gastroenteric diseases in domestic animals.
PubMed: 37859867
DOI: 10.29374/2527-2179.bjvm000723 -
Transplant Infectious Disease : An... Apr 2024We present a case of a 72-year-old liver transplant recipient 7 years prior who presents to our hospital with general malaise, fatigue, low-grade fevers, and watery...
We present a case of a 72-year-old liver transplant recipient 7 years prior who presents to our hospital with general malaise, fatigue, low-grade fevers, and watery diarrhea. He was found to have Astrovirus via PCR testing in a comprehensive stool panel. The patient's home mycophenolic acid was held upon admission, while cyclosporine was continued through his hospital stay. Generally, Astroviridae infection is a rarely identified cause of enteritis and even less so in the transplant population. Although reports have been published regarding devastating cases of encephalitis in immunocompromised patients, our patient did not exhibit these symptoms and draws into question the danger of this virus in other immunosuppressed populations. This case helps to better elucidate which patient populations should be approached with caution in the setting of Astroviridae infection.
Topics: Male; Humans; Aged; Astroviridae; Astroviridae Infections; Liver Transplantation; Diarrhea; Enteritis; Organ Transplantation
PubMed: 38407512
DOI: 10.1111/tid.14257 -
Food and Environmental Virology Mar 2024Human astroviruses (HAstVs) are a significant etiological agent of acute gastroenteritis in children. In order to investigate the circulation of HAstVs during the...
Human astroviruses (HAstVs) are a significant etiological agent of acute gastroenteritis in children. In order to investigate the circulation of HAstVs during the COVID-19 pandemic, a 2-year environmental surveillance was conducted in Jinan between 2020 and 2021. A total of 24 sewage samples were collected and concentrated. Real-time PCR indicated a positive rate of 83.3%, 79.2% (19/24), and 62.5% for classic, MLB, and VA types of HAstV in sewage samples, respectively, with genomic copies ranging from 6.4 × 10 to 3.7 × 10, 3.2 × 10 to 2.2 × 10, and 1.2 × 10 to 1.6 × 10 l. Next-generation sequencing (NGS) analysis on complete ORF2 amplicons from each sewage concentrate revealed the presence of 11 HAstV types, including HAstV-1, -2, -4, -5, MLB1, and VA1 to VA6, as well as non-human animal astroviruses. The most abundant HAstV types were HAstV-1, -4, and -5, which accounted for 70.3%, 12.6%, and 9.1% of total HAstV reads, respectively. Phylogenetic analysis revealed that the sequences obtained in this study were segregated into multiple transmission lineages, yet exhibited less genetic divergence among themselves than with foreign strains. These findings provide insight into the genotype diversity and genetic characterization of HAstVs during the COVID-19 pandemic, and highlight the effectiveness of utilizing NGS approaches to investigate sewage HAstVs.
Topics: Animals; Humans; Mamastrovirus; Sewage; Astroviridae Infections; Phylogeny; Pandemics; RNA, Viral; Genotype; Environmental Monitoring; China; COVID-19; Feces
PubMed: 38212480
DOI: 10.1007/s12560-023-09576-x