Journal of Virology最新文献

The beet necrotic yellow vein virus (BNYVV) is a multipartite virus with the highest number (up to five) of genomic segments among RNA viruses. Classified as a soil-borne virus, it is persistently transmitted by the protozoan Polymyxa betae. Previous studies have demonstrated that the relative frequency of the BNYVV genomic RNAs was modified depending on the host plant as well as the infected organ, resulting in distinct stoichiometric ratios between the viral RNAs. In this study, we investigate whether infection by the vector P. betae influences the relative abundance of BNYVV RNAs within the roots of the host plant Beta vulgaris. Furthermore, we examine the relative frequency of BNYVV genomic segments and the viral load of BNYVV at two different stages of P. betae's biological cycle: zoospore and resting spore. Our finding offers new insights into understanding the biology of this soil-borne virus and its vector. Notably, the variations in the relative accumulation of BNYVV RNAs observed in zoospores and resting spores, along with a higher viral load in zoospores compared to resting spores, invite consideration of the virus's replicative capacity within the vector.

Importance: Our understanding of the transmission of plant viruses by protozoan vectors remains poor and fragmented. The fate of viral elements in the living stages of the vector is unknown. Here, we first established a protocol allowing the purification of two forms of the vector free of cellular contaminants. This permitted the examination of the relative frequencies of beet necrotic yellow vein virus RNAs in the roots of its natural host and in two forms of its protozoan vector, Polymyxa betae, responsible for virus transmission. Our findings provide new insights into virus behavior during vector transmission, allowing us to analyze how the virus regulates its RNA frequencies and load within the vector. By focusing on the early stages of viral transmission and separating virus acquisition from transmission to new hosts, we pave the way for experiments aimed at elucidating the molecular mechanisms behind viral acquisition and the maintenance of viral genome integrity by P. betae.

The expansion of global aquaculture has brought challenges from emerging pathogens, resulting in disease-related production losses across various regions. Among these pathogens, aquatic circoviruses-small, single-stranded DNA viruses initially detected in barbel (Barbus barbus)-have now been identified in multiple aquaculture species. These viruses have been associated with various clinical manifestations in economically important fish, crustacean, and mollusk species, including acute hemorrhage syndrome, which has shown mortality rates up to 95% in controlled laboratory infections of turbot. This review consolidates current knowledge on aquatic circoviruses, focusing on their genetic diversity, epidemiology, pathogenesis, and management strategies. The analysis encompasses observed host range patterns, documented instances of cross-species transmission, and evolutionary characteristics, such as host-specific clustering and recombination events. Research gaps are highlighted, particularly in understanding viral pathogenic mechanisms, host-pathogen interactions, and their ecological roles within aquatic ecosystems. We evaluate recent advances in diagnostic methods, including targeted vaccine design and RNA interference technology. The review outlines future research priorities, including elucidating cross-species transmission potential, developing effective treatments, and assessing the full economic impact of these viruses on aquaculture. By providing a comprehensive overview, this review aims to guide future research efforts and inform strategies to mitigate the impact of circoviruses on aquaculture sustainability.

Understanding how immune history influences influenza immunity is essential for developing effective vaccines and therapeutic strategies. This study examines the antigenic imprinting of influenza hemagglutinin (HA) and neuraminidase (NA) using a mouse model with sequential infections by H1N1 virus strains exhibiting substantial antigenic differences in HA. In our pre-2009 influenza infection model, we observed that mice with more extensive infection histories produced higher levels of functional NA-inhibiting antibodies (NAI). However, following further infection with the 2009 pandemic H1N1 strain, these mice demonstrated a reduced NAI to the challenged virus. Interestingly, prior exposure to older strains resulted in a lower HA antibody response (neutralization and HAI) to the challenged virus in both pre- and post-2009 scenarios, potentially due to faster viral clearance facilitated by immune memory recall. Overall, our findings reveal distinct trajectories in HA and NA immune responses, suggesting that immune imprinting can differentially impact these proteins based on the extent of antigenic variation in influenza viruses.

Importance: Influenza viruses continue to pose a significant threat to human health, with vaccine effectiveness remaining a persistent challenge. Individual immune history is a crucial factor that can influence antibody responses to subsequent influenza exposures. While many studies have explored how pre-existing antibodies shape the induction of anti-HA antibodies following influenza virus infections or vaccinations, the impact on anti-NA antibodies has been less extensively studied. Using a mouse model, our study demonstrates that within pre-2009 H1N1 strains, an extensive immune history negatively impacted anti-HA antibody responses but enhanced anti-NA antibody responses. However, in response to the 2009 pandemic H1N1 strain, which experienced an antigenic shift, both anti-HA and anti-NA antibody responses were hindered by antibodies from prior pre-2009 H1N1 virus infections. These findings provide important insights into how antigenic imprinting affects both anti-HA and anti-NA antibody responses and underscore the need to consider immune history in developing more effective influenza vaccination strategies.

Kaposi's sarcoma herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and is associated with primary effusion lymphoma (PEL), multicentric Castleman's disease, and two inflammatory diseases. KSHV-associated cancers are primarily associated with genes expressed during latency, while other pathologies are associated with lytic gene expression. The major lytic switch of the virus, Replication and Transcription Activator (RTA), interacts with cellular machinery to co-opt the host ubiquitin proteasome system to evade the immune response as well as activate the program of lytic replication. Through stable isotope labeling using amino acids in cell culture (SILAC) labeling, ubiquitin remnant enrichment, and mass spectrometry, we have analyzed the RTA-dependent ubiquitin-modified proteome. We identified RTA-dependent changes in the populations of polyubiquitin chains, as well as changes in ubiquitinated proteins in both cells expressing RTA and naturally infected cells following lytic reactivation. We observed an enrichment of proteins that are also reported to be SUMOylated, suggesting that RTA, a small ubiquitin-like modifier (SUMO) targeting ubiquitin ligase, may function to alleviate a SUMO-dependent block to lytic reactivation. RTA targeted substrates directly through a ubiquitin ligase domain-dependent mechanism as well as indirectly through cellular ubiquitin ligase RAUL. Our ubiquitome analysis revealed an RTA-dependent mechanism of immune evasion. We provide evidence of inhibition of transporter associated with antigen processing (TAP)-dependent peptide transport, resulting in decreased human leukocyte antigen (HLA) complex stability. The results of this analysis increase our understanding of mechanisms governing the latent to lytic transition in addition to the identification of a novel RTA-dependent mechanism of immune evasion.

Importance: Kaposi's sarcoma herpesvirus, an AIDS-associated pathogen, is associated with multiple cancers and inflammatory syndromes. This virus has a latent and lytic lifecycle, each associated with pathogenesis and oncogenesis. Here, we identify proteins that display differential abundance in different phases of the lifecycle. We provide evidence supporting a new model of viral immune evasion. These findings increase our understanding of how the virus manipulates the host cell and provides new targets for intervention.

Human papillomaviruses (HPVs) travel from the trans-Golgi network (TGN) to the condensed (mitotic) chromosomes during mitosis. Partially uncoated HPV capsids utilize a unique vesicular structure for trafficking and nuclear import, which is directed by the minor capsid protein L2. However, it is still unknown which precise factors facilitate post-TGN HPV trafficking to the nucleus. Herein, we analyzed HPV16-infected mitotic cells using high-resolution microscopy, coupled with motor protein inhibition, to further elaborate on post-TGN trafficking by tracking the location and/or quantification of EdU-labeled HPV pseudogenomes on microtubules, certain kinesins, and mitotic chromosomes. We also adapted a knocksideways approach to determine if L2 and Kif11 interact in infected cells. We visualized dynein co-localization with HPV pseudogenomes along mitotic microtubules and measured HPV pseudogenome accumulation after short-term dynein inhibition. Additional inhibitor studies implicated a specific kinesin, Kif11, as participating in HPV pseudogenome delivery to the nucleus. Short-term inhibition of Kif11 decreased HPV pseudogenome accumulation at mitotic chromatin. In addition, Kif11, along with kinesins Kif18a and Kif25, were in proximity to L2 during infection. While we were unable to determine a direct interaction between L2 and Kif11, we were able to show via knocksideways approach that relocalization of exogenous Kif11 decreased HPV pseudogenome accumulation to the mitotic chromatin. Our data support a model whereby HPV16 utilizes dynein for minus-end trafficking along mitotic microtubules and utilizes Kif11 for plus-end movement in the late stage of viral entry.

Importance: Human papillomaviruses (HPV) utilize a unique vesicular structure to shield their genomes from detection during trafficking from the trans-Golgi network (TGN) to the nucleus during mitosis. The exact cellular factors responsible for trafficking these HPV genome containing vesicles along mitotic microtubules via the L2 minor protein remain unknown. We show via high-resolution microscopy that pharmacological inhibition of dynein and the kinesin Kif11 significantly decreases HPV pseudogenome accumulation on mitotic chromatin. Several kinesins were detected in proximity to incoming HPV pseudogenomes. Finally, using a novel knocksideways approach, we show reduced HPV pseudogenome accumulation on mitotic chromatin upon Kif11 relocalization to the mitochondria. Herein, our data suggest HPV utilizes minus- and plus-end mediated trafficking along mitotic microtubules to complete its genome trafficking to the nucleus.

N6-methyladenosine (m6A) is a common and dynamic epitranscriptomic modification in eukaryotic RNAs, affecting stability, splicing, translation, and degradation. Recent technological advancements have revealed the complex nature of m6A modifications, highlighting their importance in plant and animal species. The m6A modification is a reversible process, with "writers" depositing methylation, "erasers" demethylating it, and "reader" proteins recognizing m6A and executing various biological functions. Studying the relationship between m6A methylation and viral infection is crucial. Animal viruses, including retroviruses, RNA viruses, and DNA viruses, often employ the host's m6A machinery to replicate or avoid immune responses. In plant viruses, host methyltransferases or demethylases can stabilize or degrade viral RNA, depending on the virus-host interaction. Additionally, viral infections can modify the host's m6A machinery, impacting the viral life cycle. This review examines the role of m6A modifications in plant viral pathogenesis, focussing on RNA viruses infecting crops like alfalfa, turnip, wheat, rice, and potato. Understanding the role of m6A in virus-host interactions can aid in studying plant viral disease development and discovering novel antiviral targets for crop protection. In this review, we summarize current information on m6A in RNA biology, focussing on its function in viral infections and plant-virus interactions.

African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV) in pigs. Protein palmitoylation is a prevalent posttranslational lipid modification that can modulate viral replication. In this study, we investigated the palmitoylation of ASFV proteins. The results revealed that the CP123L protein (pCP123L) of ASFV was palmitoylated at the cysteine residue at position 18 (C18). To further elucidate the functional significance of this posttranslational modification, abolishing palmitoylation through a cysteine-to-serine mutation at C18 (C18S) of pCP123L (pCP123L/C18S) or treatment with 2-bromopalmitate (2-BP), a palmitoylation inhibitor, led to altered cytomembrane localization and migration rate of pCP123L. Furthermore, depalmitoylation achieved through 2-BP treatment significantly suppressed ASFV replication and exerted a profound impact on virus budding. Remarkably, blocking pCP123L palmitoylation via the C18S mutation resulted in decreased replication of ASFV. Our study represents the first evidence for the presence of palmitoylation in ASFV proteins and underscores its crucial role in viral replication.

Importance: African swine fever (ASF) poses a significant threat to the global pig industry. The causative agent of ASF is African swine fever virus (ASFV), which encodes more than 165 proteins. Protein palmitoylation, a common posttranslational lipid modification, can modulate viral infection. To date, the ASFV proteins that undergo palmitoylation and their impacts on viral replication remain elusive. In this study, the CP123L protein (pCP123L) of ASFV was identified as a palmitoylated protein, and the cysteine residue at position 18 of pCP123L is responsible for its palmitoylation. Notably, our findings demonstrate that palmitoylation plays significant roles in ASFV protein functions and facilitates viral replication.