Virology Journal最新文献

Background: Due to limitations in observational studies, the link between COVID-19 and adverse pregnancy outcomes (APOs) remains inconclusive. This study uses two-sample Mendelian randomization (MR) analyses to assess COVID-19's causal effects on APO traits.

Methods: We applied inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode to thoroughly evaluate the effects of COVID-19 infection, hospitalization, and critical status on eight APO traits.

Results: Our findings indicate that COVID-19 infection is associated with a decreased risk of eclampsia (OR: 0.35, 95%CI [0.13, 0.94]; p = 0.033) and the number of spontaneous miscarriages (OR: 0.95, 95%CI [0.91, 0.99]; p = 0.014), and an increased risk of preterm labor and delivery (OR: 1.30, 95%CI [1.04, 1.63]; p = 0.019). Hospitalized COVID-19 is associated with pre-eclampsia (OR: 1.13, 95%CI [1.00, 1.28]; p = 0.040), pre-eclampsia or eclampsia (OR: 1.14, 95%CI [1.01, 1.28]; p = 0.029), pregnancy hypertension (OR: 1.09, 95%CI [1.01, 1.18]; p = 0.021), hypertension complicating pregnancy, childbirth, and the puerperium (OR: 1.09, 95%CI [1.01, 1.18]; p = 0.021), and oedema, proteinuria, and hypertensive disorders in pregnancy, childbirth, and the puerperium (OR: 1.10, 95%CI [1.03, 1.19]; p = 0.005). Critical COVID-19 is a risk factor for pre-eclampsia or eclampsia (OR: 1.08, 95%CI [1.00, 1.17]; p = 0.044) and oedema, proteinuria, and hypertensive disorders in pregnancy, childbirth, and the puerperium (OR:1.05, 95%CI [1.00, 1.11]; p = 0.031).

Conclusions: Our study uncovered genetic evidence supporting COVID-19 as a causal risk factor for APOs, suggesting the importance of prioritizing therapeutic interventions for pregnant women infected with COVID-19 within society.

To elicit a robust immune response, an adjuvant can be combined with the antigen in influenza vaccine formulations. In this study, we evaluated the dose-sparing effect and safety of a squalene-based oil-in-water nanoemulsion (NE) adjuvant formulated with a cell culture-derived quadrivalent influenza vaccine. Immune responses-including anti-HA IgG antibody levels and hemagglutination inhibition (HAI) titers-were assessed, along with protection against a homologous challenge with influenza B virus (strain B/Maryland/15/2016 B/Victoria). We also investigated the influence of antigen dose on vaccine-induced immunity and the passive protection conferred to offspring via maternal antibody transfer. The NE adjuvant elicited strong anti-HA antibody responses in young adult mice, and these antibodies were effectively transferred from immunized mothers to their offspring. Furthermore, offspring born to NE-immunized mothers were protected against influenza virus challenge. Collectively, our results indicate that the NE formulation induces potent influenza-specific immune responses with dose-sparing effects and enables maternal transfer of protective immunity. These findings support the potential of NE as an effective adjuvant for MDCK cell-based influenza subunit vaccines. Importance. This study demonstrates that a squalene-based nanoemulsion (NE) adjuvant significantly enhances the immunogenicity and dose-sparing capacity of cell culture-derived quadrivalent influenza vaccines. Key advances include: (1) NE-adjuvanted vaccines achieved a remarkable 125-fold antigen dose reduction while maintaining antibody titers comparable to high-dose formulations, addressing critical challenges in pandemic preparedness; (2) NE induced robust humoral and cellular immunity, including elevated anti-HA IgG (10-fold increase vs. non-adjuvanted vaccine), improved HI titers, and enhanced IFN-γ/CD8 + T-cell responses; (3) Unique maternal-offspring protection was demonstrated, with transferred maternal antibodies conferring 100% survival in offspring against viral challenge. These findings position NE as an effective adjuvant technology that simultaneously optimizes antigen use and broadens immune protection across age groups.

Mumps is a highly contagious viral disease caused by the mumps virus (MuV), a member of the genus Orthorubulavirus in the family Paramyxoviridae. Although effective vaccines exist, mumps vaccination is not yet part of Uganda's routine immunization program. In 2022 and 2023, Uganda experienced a notable outbreak of mumps, underscoring the need for molecular characterization of the circulating virus strains. This study aimed to identify and genetically characterize the mumps virus strains responsible for the outbreak. Buccal or oropharyngeal swabs were collected from clinically confirmed cases from five districts. The mumps virus was isolated using the WHO Vero cell line. RNA was extracted from the isolates and clinical samples using the Qiagen kit. Real-time PCR testing was conducted and positive samples subjected to Sanger sequencing of the SH gene, a key target for genotypic classification. Phylogenetic analysis was performed using MEGA v12 software, with genotypes assigned based on phylogenetic clustering of study sequences with the 24 WHO mumps reference sequences. The study obtained ten virus isolates and fourteen sequences belonging to three genotypes: D, H and G. This genotypic variation, observed within a relatively small sample size, underscores the potential complexity of mumps virus transmission and evolution within the country. This study presents the first genetic characterization of mumps viruses from Uganda and the findings provide critical genomic baseline data for future mumps virus surveillance in Uganda, contributing to the understanding of mumps virus evolution, transmission dynamics, and potential vaccine introduction strategies.

Cervical cancer is the fourth most common cancer among women worldwide, caused by the human papillomavirus (HPV). HPV16 /18 are strongly associated with the development of cervical cancer. HPV vaccines are not widely available in economically underdeveloped areas. They also have limited efficacy against pre-existing HPV infections and cervical lesions. Therefore, the study aims to computationally design a vaccine that induces both prophylactic and therapeutic immunity against cervical cancer. Using computational approaches, we designed a multi-epitope vaccine incorporating 62 cytotoxic T lymphocyte (CTL) epitopes, 7 helper T lymphocyte (HTL) epitopes, and 3 linear B-cell epitopes from conserved regions of HPV16/18 E6, E7, and L2 proteins. To increase immunogenicity, the adjuvant RS-09 (APPHALS) was added to the N-terminal of the vaccine. The chosen CTL and HTL epitopes have the potential to achieve 100% worldwide population coverage. The vaccine candidate has appropriate physicochemical properties. The vaccine's secondary and tertiary structures were predicted, followed by refinement and validation of the models. The vaccine has a high affinity for Toll-like receptor 4 (TLR4), as indicated by its molecular docking score of -1164.4 kcal/mol and RMSD fluctuation range of 17 to 22.5 angstroms (Å) at the end of the MD simulation period. Immune response simulation showed that the vaccine candidate could induce strong humoral and cellular immune responses. The vaccine sequence's GC content was calculated to be 48.99%, and subsequently, in silico cloning of the vaccine was performed in the pET28a (+) vector. The results reveal that this vaccine is highly immunogenic; however, experimental testing is required to confirm its efficacy and safety.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen in pigs and poses a significant economic threat to the pig industry. CD163 acts as a key cellular receptor for PRRSV infection, mediating viral entry into host cells. Beyond functioning as a viral entry factor, CD163 plays multifaceted roles in PRRSV infection by linking viral pathogenesis with host immune regulation. This review summarizes current understanding of CD163's structure, physiological functions, mechanisms in PRRSV entry, and immunomodulatory roles during infection. We explore how CD163 expression and ectodomain shedding influence macrophage polarization and cytokine dynamics, thereby shaping viral persistence and tissue injury. Key evidence indicates that PRRSV harnesses anti-inflammatory signaling to sustain CD163 expression and promote entry, whereas pro-inflammatory stimuli downregulate CD163 and restrict replication. Shed soluble CD163 (sCD163) exhibits dual functions: it can act as a decoy receptor to mitigate viral spread, yet may also exacerbate inflammatory pathology. We also review recent advances in CD163-targeted interventions, including gene-edited pigs resistant to PRRSV, neutralizing antibodies, and small-molecule inhibitors that disrupt CD163-virus interactions. Critical analysis supports that targeted deletion or modification of CD163 confers viral resistance without impairing its essential physiological functions. In summary, CD163 functions not only as a gateway for PRRSV entry but also as an immunomodulator influencing disease outcomes. Elucidating this duality provides new perspectives for developing control strategies that combine effective viral blockade with the maintenance of immune homeostasis.

Background: Swine influenza virus (SIV) and porcine reproductive and respiratory syndrome virus (PRRSV) are leading pathogens in pigs, whose co-infections exacerbate disease severity. Current diagnostics like RT-PCR lack suitability for rapid, on-site use, while CRISPR-based systems face challenges in convenient multiplex detection.

Results: We developed an RT-LAMP-CRISPR-Cas12a/13a-LFD dual-detection platform that integrates reverse transcription loop-mediated isothermal amplification (RT-LAMP) with the orthogonal trans-cleavage activities of CRISPR-Cas12a and Cas13a, followed by lateral flow dipstick (LFD) visualization. This assay achieved detection limits of 5 copies/µL for SIV and 2 copies/µL for PRRSV, and exhibited high specificity against other common swine pathogens. The entire process, including a 20-minute amplification at 40 °C and 5-minute LFD readout, enables rapid and visual diagnosis. A preliminary validation was conducted using respiratory infection samples, demonstrating high concordance with reference methods and specificity against non-target pathogens.

Conclusions: The RT-LAMP-CRISPR-Cas12a/13a-LFD assay provides a sensitive, specific, and potentially field-adaptable tool for the simultaneous detection of SIV and PRRSV. It is ideally suited for early screening and precise control of these pathogens in resource-limited settings.

Background: Cucumber mosaic virus (CMV) is vectored by aphids. Infection of Arabidopsis thaliana plants with CMV affects their attractiveness to aphids (Myzus persicae) and the performance of aphids confined on these plants. CMV-induced changes in plant-aphid interactions ('viral manipulation') may promote transmission. M. persicae, an efficient CMV vector is a 'generalist', i.e., it has many plant hosts. A. thaliana is also exploited by crucifer-specialist aphids including Lipaphis erysimi (an efficient CMV vector) and Brevicoryne brassicae (a poor CMV vector). We explored the hypothesis that CMV-induced viral manipulation of aphid behaviour would exert stronger effects on M. persicae than on crucifer-specialists.

Results: M. persicae, B. brassicae and L. erysimi were released in microcosms and allowed to choose to settle on either CMV-infected or mock-inoculated plants. Initial experiments showed that as systemic CMV infection developed in A. thaliana, aphids of M. persicae were decreasingly likely to settle on infected plants. In subsequent experiments, using plants at 14 days post-infection, it was found that aphids of M. persicae were faster to choose between infected and uninfected plants than specialist aphids, but that both the generalist and specialists were less likely to settle on CMV-infected plants. Olfactometry showed that volatiles emitted by CMV-infected plants attracted M. persicae, and although the specialists showed no significant preferences, greater numbers of aphids of all three species responded when CMV-infected plant volatiles were presented to them.

Conclusions: As CMV infection develops, A. thaliana becomes less susceptible to aphid colonisation, however, plants continue to emit attractive olfactory cues. This is consistent with a model in which aphids are attracted to infected plants but discouraged from settling (e.g., by gustatory cues), which encourages aphids to carry CMV to non-infected plants. CMV appears to be more successful in manipulating the interactions of A. thaliana with the generalist aphid M. persicae, than with the crucifer specialists B. brassicae or L. erysimi.

Background: Orf is a zoonotic infectious disease caused by the Orf virus (ORFV), posing a serious threat to the health of ruminants and humans. Vaccination remains the most effective strategy for disease control. However, the limitations of conventional vaccines necessitate the development of safer and more efficient alternatives.

Methods: Based on the previously attenuated Orf vaccine strain (HB-TS09F65) as the parental virus, two gene-deletion strains, rHB09-ΔORF127 and rHB09-ΔORF130, were successfully constructed by deleting the ORF130 and ORF127 genes via homologous recombination.

Results: In vitro experiments demonstrated that both gene-deletion strains exhibited replication capacity and genetic stability comparable to their parental strains (vaccine and virulent strains). Compared with the parental strains, the two gene-deletion viruses showed reduced virulence. Immunogenicity studies of two gene-deleted virus strains demonstrated that they elicited humoral immune responses comparable to the parental virus, and significantly enhanced Th1-type cellular immune responses. Challenge experiments in a rabbit model demonstrated that rHB09-ΔORF127 and rHB09-ΔORF130 provided protection rates of 100% and 85.7%, respectively.

Conclusion: The two gene-deletion strains exhibit efficient antigen production, favorable immunogenicity, improved safety, and effective protection, making them promising candidate strains for the development of a gene-deleted vaccine against Orf.

Bacteriophages constitute a major component of the human gut virome, playing very important roles in shaping of the structure and function of the gut microbiota. Moreover, bacteriophages interact with the human immune system, thereby influencing various disease processes. Recent advancements in metagenomic sequencing and computational analysis have substantially expanded our understanding of gut phage diversity and the scale of the so-called 'viral dark matter'. In this review, we summarize current bioinformatic approaches for identifying and annotating bacteriophage sequences in metagenomic data, discuss key challenges in taxonomic classification and host prediction of phages, as well as the limitations associated with the assembly and analysis of viral metagenome-assembled genomes (vMAGs). We also analyze the therapeutic potential of bacteriophages, including their application in cancer immunotherapy, inflammatory diseases, and liver diseases, and their promise as diagnostic and prognostic biomarkers.

Background: Geminiviruses represent a significant threat to global agriculture due to the substantial crop loss they inflict worldwide. Histone chaperones, a highly conserved family of proteins primarily recognized for their roles in nucleosome assembly and disassembly, have demonstrated crucial involvement in animal virus biology. However, their contribution to the process of plant virus infection remains largely uncharacterized. To address this knowledge gap, we aimed to elucidate the role of two major histone chaperones, the replication-coupled Fasciata2 (FAS2) and the replication-independent Histone regulator A (HIRA), in the pathogenesis of geminiviruses in Nicotiana benthamiana.

Methods: We investigated the influence of histone chaperones NbHIRA and NbFAS2 during Pepper leaf curl Bangladesh virus (PepLCBV) infection within a permissive host, N. benthamiana. We employed quantitative real-time PCR (qRT-PCR) to quantify gene expression levels, discontinuous sucrose gradient assay to analyse viral minichromosome assembly, and Chromatin immunoprecipitation (ChIP) to examine histone-DNA interactions. We also evaluated both active and repressive histone methylation marks on viral minichromosomes, providing crucial insight into the regulatory influence of NbHIRA and NbFAS2 on viral gene activity.

Results: Our findings indicate that downregulation of NbHIRA and NbFAS2 leads to an increase in virus transcript accumulation. The virus may utilize the elevated NbRAD51 levels in the knockdown plants, contributing to the increased viral load. Conversely, overexpression of both NbHIRA and NbFAS2 exerts a significant antiviral effect, resulting in the reduction of virus transcripts in both local as well as distal plant tissues. This observed decrease in viral titre linked to a high degree of compaction of virus minichromosomes. Concurrently, these compacted virus minichromosomes exhibit an increase in accumulation of repressive histone mark H3K9me2, rendering them less virulent compared to wild-type virus minichromosomes.

Conclusions: Overexpression of NbHIRA and NbFAS2 significantly boosts antiviral activity against geminivirus infections by altering the structure of virus minichromosomes. Consequently, these findings propose that targeting histone chaperones such as NbHIRA and NbFAS2 could offer a promising strategy for managing geminivirus-related infections in crop plants and agricultural applications.