Virology最新文献

Porcine reproductive and respiratory syndrome (PRRS) significantly impacts the global swine industry. Sichuan province, a key pig breeding center in China, has limited data on the molecular epidemiology of PRRS Virus (PRRSV). To address this, 1618 suspected PRRSV samples were collected from 2021 to 2023, with a prevalence rate of 39.74% (643/1618). Phylogenetic analysis showed PRRSV-2 as dominant (95.65%, 615/643), with PRRSV-1 at 4.35% (28/643). PRRSV-2 strains were further classified into NADC30-like (74.18%), NADC34-like (11.98%), C-PRRSV (5.44%), and HP-PRRSV (4.04%). The significant change in the proportions of different lineages indicates genomic divergence. NADC30-like strains exhibited significant amino acid mutations in ORF5, aiding immune evasion. Recombination analysis revealed complex patterns, primarily involving NADC30-like strains. This study highlights the genomic divergence of PRRSV in Sichuan, with NADC30-like strains becoming predominant and emerging strains like NADC34-like showing potential for further spread.

In response to the problems associated with drug resistance resulting from the use of antibiotics, phages have become desirable options for the treatment of Vibrio alginolyticus disease in aquaculture. In this study, we isolated a novel double-stranded DNA (dsDNA) phage named vB_ValC_WD615 infecting V. alginolyticus; this phage belongs to the family Podoviridae and has a short noncontractile tail (13 ± 1.5 nm) and an icosahedral head (60.2 ± 2 nm); its genome is 50,522 bp and encodes 69 open reading frames (ORFs) and no lysogenic genes were annotated in the genome. Physiological results indicate that vB_ValC_WD615 infects V. alginolyticus SC1 with a burst size of 335 PFU/cell and can maintain stable infectivity within temperature and pH conditions ranging from 4 to 45 °C and 3 to 11, respectively. The results suggest that the vB_ValC_WD615 isolated from coastal waters could be a potential candidate for phage therapy targeting V. alginolyticus.

The global rise of oropharyngeal cancers (OPC) associated with the human papillomavirus (HPV) type 16 necessitates a deeper understanding of their underlying molecular mechanisms. Our study utilised RNA-sequencing data from The Cancer Genome Atlas (TCGA) to identify and analyse differentially expressed (DE) long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in HPV16-positive OPC, and to elucidate the interplay within the lncRNA/miRNA/mRNA regulatory network. We revealed 1929 DE lncRNAs and identified a significant expression shift in 37 of these, suggesting a regulatory 'sponge' function for miRNAs that modulate cellular processes. Notably, the lncRNA Linc00911 exhibited decreased expression in HPV16-positive OPC, a change directly attributable to HPV oncogenes E6 and E7 as confirmed by RT-qPCR in cell lines and patient samples. Our comprehensive analysis presents an expansive landscape of ncRNA-mRNA interactions, offering a resource for the ongoing pursuit of elucidating the molecular underpinnings of HPV-driven OPC.

Infectious laryngotracheitis (ILT) is a respiratory disease affecting chickens worldwide. Unlike many countries, Switzerland does not vaccinate against ILT. This study analysed ILT samples from 21 natural outbreaks in Switzerland using restriction fragment length polymorphism (RFLP) and multiple gene sequencing. Chicken embryo origin (CEO) and tissue culture origin (TCO) vaccine strains were included as references. Both vaccine strains were distinguishable, and 14 out of 21 samples resembled the CEO vaccine. Additionally, four distinct non-vaccine-like groups were identified. Sequencing of three genes from selected Swiss samples and those from neighbouring countries revealed four phylogenetic clades. Notably, four Swiss field strains formed two unique clades, not closely related to vaccine strains or ILTV from neighbouring countries. Overall, RFLP results were supported by sequencing data. This study demonstrates the presence of both vaccine-like and wild-type ILT viruses in Switzerland, where vaccination is de facto prohibited.

Human Papillomavirus serotype 16 (HPV16) capsid protein (L1) pentamers canonically assemble into T = 7 icosahedral capsids. Such virus-like particles are the basis of the HPV vaccine. We examined assembly of L1 pentamers in response to pH, mild oxidants, and ionic strength and found a mixture of closed, roughly spherical structures from ∼20 to ∼70 nm in diameter, indicating the presence of many kinetically accessible energy minima. Using bulk and single particle techniques we observed that the size distribution changes but does not reach homogeneity. Though heterogenous in size, particles showed uniform responses to low ionic strength dissociation, thermal unfolding, and susceptibility to protease digestion. These assays suggest maturation over time, but at different rates. Cysteine oxidation further stabilized particles at early, but not late, times without changing general characteristics including thermal stability and protease digestion. These data show complex assembly paths to species of different sizes, but with locally similar interactions.

Emerging viruses, such as novel influenza A viruses (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose a constant threat to animal and human health. Identification of host cell factors necessary for viral replication but dispensable for cellular survival might reveal novel, attractive targets for therapeutic intervention. Proteolytic activation of IAV hemagglutinin (HA) and SARS-CoV-2 spike protein (S) by the type II transmembrane serine protease (TTSPs), e.g. TMPRSS2 is sought to be critical for viral spread and pathogenesis. Here, we investigated the secondary structure of TMPRSS2 mRNA coding sequence and designed TMPRSS2-specific antisense oligonucleotides (ASOs). Several of these ASOs markedly reduced the TMPRSS2 expression and decreased IAV infection and SARS-CoV-2 entry into cells.

Viruses enter the host cell, and various strategies are employed to evade the host immune system. These include overcoming the various components of the immune system, including modulation of the physical and chemical barriers, non-specific innate response and specific adaptive immune response. Morbilliviruses impose immune modulation by utilizing various approaches including hindering antigen presentation to T-Helper (T_H) cells, hematopoiesis and suppression of effector molecule activities. These viruses can also impede the early stages of T cell activation. Despite the availability of effective vaccines, morbilliviruses are still a significant threat to mankind. After infection, they also induce a state of immune suppression in the host. The molecular mechanisms employed by morbilliviruses to induce the state of immune suppression in the infected host are still being investigated. This review is an attempt to summarize insights into some of the strategies adopted by morbilliviruses to mediate immune modulation in the host.

Emerging evidence suggests that the localization of viral movement proteins (MPs) to both plasmodesmata (PD) and viral replication complexes (VRCs) is the key to viral cell-to-cell movement. However, the molecular mechanism that establishes the subcellular localization of MPs is not fully understood. Here, we investigated the PD localization pathway of red clover necrotic mosaic virus (RCNMV) MP and the functional regions of MP that are crucial for MP localization to PD and VRCs. Disruption analysis of the transport pathway suggested that RCNMV MP does not rely on the ER-Golgi pathway or the cytoskeleton for the localization to the PD. Furthermore, mutagenesis analysis identified amino acid residues within the alpha helix regions responsible for localization to the PD or VRCs. These α-helix regions were also essential for efficient viral cell-to-cell movement, highlighting the importance of these dynamic localization of the MPs for viral infection.

Pseudorabies virus is a swine alpha-herpesvirus. We demonstrated that alpha-herpesvirus infection downregulates HSF1, a master transcription factor in the heat shock response. The serine/threonine protein kinase activity of late viral protein UL13 is indispensable for HSF1 depletion and phosphorylation, and UL13 does not degrade HSF1 posttranslationally but inhibits the HSF1 mRNA level. Importantly, UL13 increased HSF1 activity even though it reduced HSF1 mRNA. Furthermore, viral replication markedly decreased in the HSF1 knockout cell line or in the presence of an HSF1-specific inhibitor. Interestingly, HSF1 knockout accelerated the activation of NF-κB and p38MAPK. The K96 loci of UL13 are important to induce high levels of IL-6, TNF-α, and IL-β cytokines while playing a crucial role in promoting mild interstitial pneumonia, liver necrosis, and severe inflammatory cell infiltration in the footpad. Thus, UL13 steers the heat shock response to promote viral replication and the inflammatory response.

Importance

PRV is a ubiquitous pathogen that infects a variety of mammals, such as pigs, ruminants, carnivores, and rodents as well as human beings, causing enormous economic losses in the swine industry. Here, we employed PRV as a model to determine the relationship between α-herpesvirus and the inflammatory response. Overall, our findings indicated that PRV infection inhibits the level of HSF1 mRNA via the serine/threonine protein kinase activity of UL13. Additionally, we discovered that HSF1 was involved in NF-κB activation upon PRV infection. PRV UL13 orchestrates the level of HSF1 mRNA, HSF1 protein phosphorylation, and priming of the inflammatory response. Our study reveals a novel mechanism employed by UL13 serine/threonine protein kinase activity to promote the inflammatory response, providing novel clues for therapy against alpha-herpesvirus infection.

Kitaviruses are plant-infecting, non-systemic disease-causing viruses with multipartite single-stranded RNA genomes. Despite their importance, knowledge on kitaviruses is limited in comparison with other plant virus groups, mainly because of the lesser number of identified and characterized kitaviruses and their isolates. In the present study, we explored plant (meta)transcriptome data available in public domain and identified genome sequences of eighteen putative novel blunerviruses in eighteen plant species, including four gymnosperm and four monocot species. Four RNA segments (RNAs 1–4) of eleven identified viruses were recovered, whilst at least two RNA segments were recovered for the remaining viruses. Phylogenetic analysis grouped the identified viruses with known blunerviruses. Based on genome organization, sequence identities of encoded proteins with known blunerviruses and phylogeny, the identified viruses are regarded as new members of the genus Blunervirus. The study paves way for initiating further studies on understanding biological properties, economic importance and geographical distribution of identified blunerviruses.