Viruses-Basel最新文献

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Background: There is scarce information on Varicella-Zoster virus genetic variability in individuals with acute central nervous system infection in Brazil. The objective of this study was the molecular characterization of Varicella-Zoster virus isolates in cerebrospinal fluid from individuals with acute central nervous system infection.

Methods: Cerebrospinal fluid samples were collected from individuals evaluated in emergency and community healthcare services in São Paulo, Brazil. Varicella-Zoster virus identification was performed using commercial platforms Biofire-FilmArray Meningitis/Encephalitis (BioMérieux, Craponne, France) and XGEN-UMLTI-N9^® (Mobius Life, Pinhais, Brazil). Positive samples were further characterized as wild-type or vaccine-strain by a real-time polymerase chain reaction assay that targeted a single nucleotide polymorphism in open reading frame 62. We also estimated the mean genetic distance and phylogenetic reconstruction based on open reading frames 22, 38, 54, and 62 in relation to sequences of intercontinentally circulating Varicella-Zoster virus isolates.

Results: Among the 600 cerebrospinal fluid samples, we identified Varicella-Zoster virus in 30 (5%) samples. None were positive for the vaccine-strain. Twelve samples were sequenced and phylogenetically classified into Clades 1 (41.7%), 2 (25%), 3 (8.3%), 5 (16.7%), or 6 (8%).

Conclusion: Enhanced characterization of circulating Varicella-Zoster virus Clades in Brazil identified previously unreported Clades 2 and 6 as well as three other Clades disseminated intercontinentally. These findings reinforce the importance of Varicella-Zoster virus molecular surveillance in cerebrospinal fluid.

Heart and skeletal muscle inflammation (HSMI) is a significant disease affecting Atlantic salmon (Salmo salar) production in Norway but has had limited impact to production in North America. The causative agent of HSMI is piscine orthoreovirus genotype 1 (PRV-1), and disease variation between regions is suggested to be at least partially driven by genetic variation of the virus. Using controlled laboratory injection challenges, we corroborate variations in disease outcomes for three PRV-1 isolates (PRV-1a from the eastern Pacific, PRV-1a from the western Atlantic, and PRV-1b from the Norwegian sea); however, virus replication dynamics, host recognition, and PRV-1-associated heart inflammation were also discrete relative to the Atlantic salmon stock challenged, irrespective of the viral isolate used. Specifically, New Brunswick Tobique River Atlantic salmon had less (p < 0.01) heart inflammation relative to Mowi-McConnell Atlantic salmon of Western Canada which, in turn, had less (p < 0.01) heart inflammation than Mowi Atlantic salmon of Scotland when cumulatively considering challenges using all three PRV-1 isolates. These data indicate that the presence of PRV-1a or PRV-1b alone is not sufficient to reliably predict disease and highlights at least one potential mechanism (host genotype) for reducing HSMI disease severity.

Post-translational modifications (PTMs) serve as critical regulators of protein function across biological systems, including during viral infection. For orthoflaviviruses, including human pathogens like dengue, Zika, and West Nile viruses, PTMs on viral proteins regulate multiple aspects of the viral lifecycle and pathogenesis. Here, we review the mechanisms by which PTMs regulate orthoflavivirus infection in both vertebrate and arthropod hosts. We examine how ubiquitination and glycosylation on the viral envelope proteins facilitate viral entry and how phosphorylation, SUMOylation, and acetylation on non-structural proteins modulate viral RNA replication. Additionally, we describe how PTMs on viral structural proteins dynamically regulate viral assembly and egress. We also describe how PTMs can influence tissue tropism and host-specific pathogenesis, with some modifications showing divergent functions between arthropod vectors and vertebrate hosts, and how the host antiviral response can trigger specific PTMs on viral proteins to restrict infection, highlighting PTMs as key mediators of host-pathogen interactions. While significant progress has been made in identifying PTMs on viral proteins, many questions remain about their temporal dynamics, mechanisms of action, and conservation across the orthoflavivirus genus. Understanding how PTMs regulate orthoflavivirus infection may reveal new therapeutic strategies, particularly given recent advances in targeting specific protein modifications for disease treatment.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that, since its re-emergence in 2004, has become recognised as a major public health concern throughout many tropical and sub-tropical regions of the world. Amongst the insights gained from studies on other alphaviruses, several key determinants of virulence have been identified, including one present at the P3 position in the nsP1/nsP2 cleavage domain of the S.A.AR86 Sindbis (SINV) strain. This strain is associated with neurovirulence in adult mice; however, when a threonine-to-isoleucine substitution is engineered at this P3 position, an attenuated phenotype results. A reverse genetics system was developed to evaluate the phenotype that resulted from the substitution of alanine, present at the P3 position in the wild-type CHIKV clone, with valine. The A533V-mutant CHIKV induced milder disease symptoms in the C57BL/6 mouse model than the wild-type virus, in terms of severity of inflammation, length of viraemic period, and histological changes. Furthermore, the induction of type I IFN occurred more rapidly in both CHIKV-infected cell cultures and the mouse model with the mutant CHIKV.

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a severe hemorrhagic disease with a mortality rate reaching 100%. Despite extensive research on ASFV mechanisms, no safe and effective vaccines or antiviral treatments have been developed. Live attenuated vaccines generated via gene deletion are considered to be highly promising. We developed a novel recombinant ASFV strain by deleting MGF360-10L and MGF505-7R, significantly reducing virulence in pigs. In the inoculation experiment, pigs were infected with 10⁴ 50% hemadsorption doses (HAD₅₀) of the mutant strain. All the animals survived the observation period without showing ASF-related clinical signs. Importantly, no significant viral infections were detected in the cohabitating pigs. In the virus challenge experiment, all pigs succumbed after being challenged with the parent strain. RNA-seq analysis showed that the recombinant virus induced slightly higher expression of natural immune factors than the parent ASFV; however, this level was insufficient to provide immune protection. In conclusion, our study demonstrates that deleting MGF360-10L and MGF505-7R from ASFV CN/GS/2018 significantly reduces virulence but fails to provide protection against the parent strain.

The communities of viruses studied in rabbits and hares (family Leporidae) have largely been those with clinical significance. Consequently, less is known broadly about other leporid viruses. Anelloviruses (family Anelloviridae) are likely commensal members of the single-stranded DNA virome in mammals. Here, we employ a viral metagenomic approach to identify DNA viruses of leporids and the ticks feeding on them in Arizona, USA. We characterize five complete anellovirus genomes from four leporids belonging to the black-tailed jackrabbit (Lepus californicus, n = 3) and the desert cottontail (Sylvilagus audubonii, n = 1). All five anellovirus genomes share > 69% orf1 gene pairwise nucleotide identity with those found in Iberian hares and thus belong to the species Aleptorquevirus lepor1. Accordingly, we expand the known host range of this anellovirus species to include Iberian hares in Europe and black-tailed jackrabbit and desert cottontail in the USA. We also sequenced the complete mitochondrial genomes of the four leporid hosts (Sylvilagus audubonii, n = 1; Lepus californicus, n = 3) and two ticks (Dermacentor parumapertus, n = 2) found feeding on two black-tailed jackrabbits. These results expand the diversity of anelloviruses in leporids while giving insight into the host genetics of leporids and ticks in Arizona, USA.

The nucleocytoplasmic transport of proteins using XPO1 (exportin 1) plays a vital role in cell proliferation and survival. Many viruses also exploit this pathway to promote infection and replication. Thus, inhibiting the XPO1-mediated nuclear export pathway with selective inhibitors has a diverse effect on virus replication by regulating antiviral, proviral, and anti-inflammatory pathways. The XPO1 inhibitor Selinexor is an FDA-approved anticancer drug predicted to have antiviral or proviral functions against viruses. Here, we observed that the pretreatment of cultured cell lines from human or mouse origin with the nuclear export inhibitor Selinexor significantly enhanced the protein expression and replication of mouse hepatitis virus (MHV), a mouse coronavirus. The knockdown of cellular XPO1 protein expression also significantly enhanced the replication of MHV in human cells. However, for SARS-CoV-2, Selinexor treatment had diverse effects on virus replication in different cell lines. These results indicate that XPO1-mediated nuclear export pathway inhibition might affect coronavirus replication depending on cell types and virus origin.

Ostreid herpesvirus 1 (OsHV-1) infection is the primary viral disease responsible for large-scale mortality in bivalve mollusks worldwide, and effective strategies to control the outbreaks of this disease are still lacking. Berberine (BBR), a plant-derived alkaloid, has demonstrated antiviral activity against various vertebrate viruses, while its potential antiviral effects on molluscan herpesviruses remain to be fully elucidated. Therefore, the present study sought to investigate the potential of berberine hydrochloride (BBH) against OsHV-1 infection in blood clams (Anadara broughtonii). The most optimal BBH concentration was figured out according to virus replication and mortality rates during in vivo experimental infection. Quantitative PCR and reverse transcription quantitative PCR were utilized to monitor the OsHV-1 genomic copy numbers and viral gene transcription levels during the development of OsHV-1 infection in the BBH-treated and control groups. The results demonstrated that a 3 mg/L BBH bath immersion significantly suppressed OsHV-1 replication in blood clams. During the early stage of infection (24 h), BBH treatment significantly reduced the expression of OsHV-1 open reading frames (ORFs) related to early enzymes, putative membrane proteins, and nucleocapsid proteins. At 96 h post-infection, all untreated blood clams died, whereas the survival rate of BBH-treated individuals increased to 46.67%. This study provides preliminary evidence for the inhibitory effects of BBH on OsHV-1, paving the way for the development of pharmacological control technologies for OsHV-1 infections.