Viruses-Basel最新文献

H5N1 is a highly pathogenic avian influenza virus of major global concern. Since 2023, it has circulated widely among wild and farmed birds, with increasing spillover into mammals, including minks, seals, and cattle, and sporadic infections in humans in Chile, the UK, and the USA. The risk of a future pandemic is considered high because ongoing viral evolution could enable efficient human-to-human transmission. The hemagglutinin (HA) glycoprotein is the principal determinant of host range, mediating viral attachment and entry through interactions with sialylated glycans and potentially additional host surface proteins. Here, we developed an artificial intelligence (AI)-based pipeline integrating structural modeling, protein-protein interaction prediction, and biological filtering to identify human cell surface proteins with high likelihood of interacting with H5N1 HA. These interactions may contribute to viral entry and tropism and therefore represent promising candidates for experimental validation and therapeutic targeting. Our findings highlight the utility of AI-driven pipelines in accelerating the discovery of host factors relevant to pandemic influenza viruses.

During the COVID-19 pandemic (which some argue is still ongoing), I led three Special Issues (SIs) that were designed to cover the talking points that arose amongst many practitioners and researchers: (1) How can we maintain our usual diagnostic services in the face of an ongoing pandemic [...].

Interferon-stimulated genes (ISGs) were initially discovered for their role in antiviral functions. However, recent studies show evidence of a diverse and context-specific regulatory function of these genes in antiviral and antibacterial protection. The molecular mechanisms of such activities vary depending on the pathogen, cell type, isoform, and species. In this review, we summarize the context-specific functions of several prominent and well-known ISG families, including OAS, IFITs, ISG15, viperin, ADAR1, and Mx proteins. We provide examples of distinct enzymatic or regulatory mechanisms that are employed by these ISGs to carry out their diverse functions, including nucleic acid sensing, RNA degradation, translation inhibition, membrane remodeling, etc.

We describe RNA-Seq analyses conducted on nasopharyngeal swabs collected from 37 patients admitted to an Australian intensive care unit from October 2022 to August 2023. During this time, the dominant omicron sublineage infections broadly progressed from BA.5 to BA.2-like, to XBB-like, then XBC, consistent with global trends. Viral load and patient metadata correlations indicated this cohort was broadly representative of severe COVID-19 patients. Human gene expression analyses were complicated by the large range (>5 log) and variability in viral reads. Nevertheless, the comparison of XBC and BA.5 samples that had comparable viral read counts, revealed differentially expressed genes and a cellular deconvolution signature that indicated increased targeting of ciliated epithelial cells by XBC. To obtain more evidence for increased targeting of ciliated epithelial cells by the later omicron sublineage viruses, a series of mouse strains were infected with a BA.5 or a XBB isolate. Increased infection of the nasal turbinates and ciliated epithelial cells by XBB was demonstrated by viral titrations and immunohistochemistry, respectively. Compared with previous lineages, the omicron lineage showed increased targeting of ciliated epithelia in the upper respiratory tract, with the data presented herein suggesting this trend continued for the omicron sublineages.

Vectoring tomato spotted wilt virus (TSWV) by two well-known thrips species, Frankliniella occidentalis Pergande and F. intonsa Trybom (Thysanoptera: Thripidae), is facilitated in different ways. Symbiotic bacteria positively influence thrips fitness, but the interaction between these bacteria and tospovirus inside the thrips' body remains unknown. Metagenomic profiling of symbionts in nonviruliferous and viruliferous Frankliniella thrips was performed to elucidate the interactions between symbiotic bacteria and the virus. A total of 97 operational taxonomic units (OTUs) were identified by profiling the microbes, where Proteobacteria was the most abundant phylum, with a high richness in Serratia spp. F. occidentalis showed lower variation in bacterial diversity between nonviruliferous and viruliferous treatments than F. intonsa. RT-qPCR validation for Serratia and Escherichia revealed opposite abundance patterns between the two thrips species. In contrast, Enterobacteriaceae and Pantoea showed similar patterns with higher abundance in nonviruliferous conditions. Wolbachia was detected exclusively in F. intonsa, with a higher bacterial titer in the viruliferous sample. Our findings suggest that TSWV association may influence the abundance of different bacterial symbionts within the thrips' body, potentially via induction of antimicrobial peptides in response to viral invasion, and to our knowledge this is the first report addressing this tripartite interaction. These findings improve our understanding of how virus-symbiont association contributes to thrips vector competence.

Post-COVID cardiac complications have emerged as a significant and persistent clinical concern, yet their underlying mechanisms remain poorly understood. Animal models can act as proxies to investigate the pathophysiology of the human, post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this experimental study was to evaluate the expression of inflammatory biomarkers in cardiac tissue 28 days after SARS-CoV-2 infection in a female hACE2 mouse model, with a focus on chemokine-mediated immune activation. Twelve female C57BL/6 hACE2 mice were infected with the Omicron variant (BA.1.17 lineage) of SARS-CoV-2, and eleven non-infected mice served as controls. Cardiac tissue was analyzed via Western blot for markers of innate immune activation (TLR4, MyD88, NF-κB) and pro-inflammatory cytokines (IL-6, IL-18, IL-1β, TNF-α, CD11d). Cardiac tissue injury markers (iNOS, PAI-1 and Connexin43) were also analyzed. Compared to non-infected mice, cardiac tissue from infected mice showed significantly higher expression of IL-6 (p = 0.028), indicating an inflammatory state, and CD11d (p = 0.016), suggesting an inflammatory stage accompanied by sustained activation of chemokine-mediated inflammatory signaling. No significant differences in TLR4 (p = 0.340), MyD88 (p = 0.410), NF-κB p65 (p = 0.780), IL-18 (p = 0.548), IL-1β (p = 0.455), and TNF-α (p = 0.125) expressions were observed Similarly, no changes in cardiac damage markers (iNOS: p = 0.4684; PAI-1: p = 0.5345; Connexin 43: p = 0.2879) were found. The results of this experimental study would support the hypothesis of persistent low-grade inflammation as a contributor to post-COVID cardiac sequelae in females that is not accompanied by severe tissue damage, as also observed in clinical studies. This study also reinforces the need for studies evaluating the functional and structural evolution of the myocardium after an acute SARS-CoV-2 infection.

Bacteriophage therapy is regarded as a promising alternative for treating and preventing antibiotic-resistant bacterial infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent and difficult-to-treat pathogens. S. aureus also contributes to the formation of both single- and mixed-species biofilms. Treating biofilms remains a major challenge for antibiotic-based eradication of pathogens, as the biofilm matrix provides a protective barrier for bacteria. The selection of highly active phages targeting S. aureus is therefore crucial for medical applications, given the high prevalence and drug resistance of this pathogen. In this study, S. aureus phage vB_SaS_GE1 (GE1) was isolated and characterized as a potential therapeutic agent. The phage was isolated and propagated, and its host range was determined using standard methods. Whole-genome sequencing and annotation of the phage DNA were performed. A time-kill assay and evaluation of the anti-biofilm activity of the Staphylococcus phage, both alone and in combination with Pseudomonas phage GEC_PNG3 (PNG3) on mixed-species biofilms, were conducted. The results indicated that GE1 is a lytic phage that does not carry virulence-determining genes. The time-kill assay demonstrated sustained lytic activity of GE1 without the emergence of phage-resistant mutants in the tested MRSA strains. Although phage treatment increased biofilm matrix production compared to the control, the viable cell count within the biofilms was reduced. Overall, the characteristics assessed indicate that vB_SaS_GE1 is safe and exhibits strong antibacterial activity against MRSA strains.

Background: During the COVID-19 pandemic, high rates of infection with SARS-CoV-2 were reported in healthcare workers (HCWs), among whom asymptomatic individuals had high potential to spread the virus while assisting high-risk patients. This study conducted routine SARS-CoV-2 screening among the staff of a specialized cardiology hospital in Brazil during 2022 and 2023, while also evaluating variables associated with infection and the occurrence of symptoms.

Methods: A prospective cohort study of 94 HCWs with biweekly RT-PCR screening was performed, employing RT-PCR from nasal swabs.

Results: Participants aged 50.9 ± 10.2 years and were predominantly female (85.1%) and non-white (56.4%). The follow-up period was 576.4 ± 185.9 days, and most participants worked in the intensive care unit/emergency department (34%). Although the HCWs with the highest COVID-19 rates before inclusion were technicians/graduates (67.3%) and non-white individuals (57.7%), these groups presented lower infection rates at follow-up (p < 0.001, CI 95% 2.924-27.93; and p = 0.02, CI 95% 0.129-0.859, respectively). The number of asymptomatic cases increased during the study (p = 0.001), and simultaneous infection upsurges occurred in different hospital departments.

Interpretation: These data highlight the association between educational level and the risk of SARS-CoV-2 infection in HCWs. The synchronicity of cases in different hospital departments offers insights about the nosocomial spread of SARS-CoV-2. The increase in the number of asymptomatic infections with repeated infections suggests that regular molecular screening may contribute to increasing the safety of both patients and HCWs in a pandemic context.

Supramolecular proteins have emerged as promising templates for guiding metal ion mineralization into well-defined nanomaterials because of their structural versatility and chemical diversity. However, the precise control of metal ion nucleation on the different reactive sites of protein templates remains challenging. In this study, a genetically engineered hollow tobacco mosaic virus protein fiber (TMVF) with excellent structural stability was employed to achieve selective mineralization of noble metal nanostructures either on its external surface or within its internal channel. Moreover, the Pt/Pd bimetallic nanowire (NW) was also successfully prepared by co-depositing Pt and Pd on the TMVF. The bimetallic NWs demonstrated a peroxidase-like activity, which enabled their application for cholesterol detection by cooperating with cholesterol oxidase.

The increasing proportion of HIV-1 infections transmitted via non-marital non-commercial heterosexual contact (NMNCHC) in China necessitates a deeper understanding of its local characteristics. This study investigated the epidemiological, molecular network, and drug-resistant profiles among 400 newly diagnosed HIV-1 patients infected via non-marital heterosexual contact (NMHC), specifically its non-commercial subtype, in Lishui from 2020-2024. HIV-1 pol gene sequences were analyzed for subtypes, drug resistance mutations, and transmission clusters using phylogenetic and network methods (genetic distance threshold: 0.9%). The overall prevalence of transmitted drug resistance (TDR) was 13.3%, an intermediate level exceeding the national average, driven predominantly by NNRTI resistance (6.3%). High-level resistance to NVP (3.0%) and EFV (2.75%) was observed. CRF08_BC (43.8%) was the dominant subtype. Multivariate analysis identified female gender and higher education as significant risk factors for NMNCHC acquisition. Molecular network analysis incorporated 55.3% of cases, revealing clusters predominantly composed of middle-aged and elderly males, with CRF08_BC and CRF01_AE showing higher NMNCHC transmission risk within networks. These findings underscore an evolving epidemic with significant TDR and highlight the urgent need for targeted interventions, including enhanced resistance surveillance and focused strategies for the concealed NMNCHC population, to curb local HIV-1 transmission.