Effect of Killed PRRSV Vaccine on Gut Microbiota Diversity in Pigs

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting the global swine industry. Vaccination is still a main strategy for PRRSV control; however, host factors associated with vaccine efficacy remain poorly understood. Growing evidence suggests that mucosa-associated microbiomes may play a role in the responses to vaccination. In this study, we investigated the effects of a killed virus vaccine on the gut microbiome diversity in pigs. Fecal microbial communities were longitudinally assessed in three groups of pigs (vaccinated/challenged with PRRSV, unvaccinated/challenged with PRRSV, and unvaccinated/unchallenged) before and after vaccination and after viral challenge. We observed significant interaction effects between viral challenge and vaccination on both taxonomic richness and community diversity of the gut microbiota. While some specific taxonomic alterations appear to be enhanced in vaccinated/challenged pigs, others appeared to be more consistent with the levels in control animals (unvaccinated/unchallenged), indicating that vaccination incompletely protects against viral impacts on the microbiome. The abundances of several microbial taxa were further determined to be correlated with the level of viral load and the amount of PRRSV reactive CD4⁺ and CD8⁺ T-cells. This study highlights the potential roles of gut microbiota in the response of pigs to vaccination, which may pave the road for the development of novel strategies to enhance vaccine efficacy.     

Global Extension and Predominance of Human Metapneumovirus A2 Genotype with Partial G Gene Duplication

Human metapneumovirus (HMPV) is an important respiratory pathogen and is divided in two main groups (A and B). HMPV strains with partial duplications (111-nt and 180-nt duplication) of the G gene have been reported in recent years. Since the initial reports, viruses with these characteristics have been reported in several countries. We analyzed all complete HMPV G gene ectodomain sequences available at GenBank to determine if viruses with 111-nt or 180-nt duplication have become the leading HMPV strains worldwide, and to describe their temporal and geographic distribution. We identified 1462 sequences that fulfilled study criteria (764 HMPV A and 698 HMPV B) reported from 37 countries. The most frequent HMPV A genotype was A2b2 (n = 366), and the most frequent B genotype was B2 (n = 374). A total of 84 sequences contained the 111-nt duplication, and 90 sequences contained the 180-nt duplication. Since 2016, viruses with a partial duplication comprise the most frequent HMPV A sequences globally and have displaced other HMPV A viruses in Asia, Europe, and South America; no sequences of viruses with partial duplication have been reported in North America or Africa so far. Continued surveillance of HMPV is required to identify the emergence and spread of epidemiologically relevant variants.     

PRRSV Induces HMGB1 Phosphorylation at Threonine-51 Residue to Enhance Its Secretion

Porcine reproductive and respiratory syndrome virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1) to mediate inflammatory response that is involved in the pulmonary injury of infected pigs. Our previous study indicates that protein kinase C-delta (PKC-delta) is essential for HMGB1 secretion in PRRSV-infected cells. However, the underlying mechanism in HMGB1 secretion induced by PRRSV infection is still unclear. Here, we discovered that the phosphorylation level of HMGB1 in threonine residues increased in PRRSV-infected cells. A site-directed mutagenesis study showed that HMGB1 phosphorylation at threonine-51 was associated with HMGB1 secretion induced by PRRSV infection. Co-immunoprecipitation (co-IP) of HMGB1 failed to precipitate PKC-delta, but interestingly, mass spectrometry analysis of the HMGB1 co-IP product showed that PRRSV infection enhanced HMGB1 binding to ribosomal protein S3 (RPS3), which has various extra-ribosomal functions. The silencing of RPS3 by siRNA blocked HMGB1 secretion induced by PRRSV infection. Moreover, the phosphorylation of HMGB1 at threonine-51 was correlated with the interaction between HMGB1 and RPS3. In vivo, PRRSV infection also increased RPS3 levels and nuclear accumulation in pulmonary alveolar macrophages. These results demonstrate that PRRSV may induce HMGB1 phosphorylation at threonine-51 and increase its interaction with RPS3 to enhance HMGB1 secretion. This finding provides insights into the pathogenesis of PRRSV infection.     

Point-of-Care and Label-Free Detection of Porcine Reproductive and Respiratory Syndrome and Swine Influenza Viruses Using a Microfluidic Device with Photonic Integrated Circuits

Swine viral diseases challenge the sector’s sustainability by affecting productivity and the health and welfare of the animals. The lack of antiviral drugs and/or effective vaccines renders early and reliable diagnosis the basis of viral disease management, underlining the importance of point-of-care (POC) diagnostics. A novel POC diagnostic device utilizing photonic integrated circuits (PICs), microfluidics, and information and communication technologies for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza A (SIV) was validated using spiked and clinical oral fluid samples. Metrics including sensitivity, specificity, accuracy, precision, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the performance of the device. For PRRSV, the device achieved a sensitivity of 83.5%, specificity of 77.8%, and DOR values of 17.66, whereas the values for SIV were 81.8%, 82.2%, and 20.81, respectively. The POC device and PICs can be used for the detection of PRRSV and SIV in the field, paving the way for the introduction of novel technologies in the field of animal POC diagnostics to further optimize livestock biosecurity.     

Efficacy of the Sentinox Spray in Reducing Viral Load in Mild COVID-19 and Its Virucidal Activity against Other Respiratory Viruses: Results of a Randomized Controlled Trial and an In Vitro Study

Sentinox (STX) is an acid-oxidizing solution containing hypochlorous acid in spray whose virucidal activity against SARS-CoV-2 has been demonstrated. In this paper, results of a randomized controlled trial (RCT) on the efficacy of STX in reducing viral load in mild COVID-19 patients ({"type":"clinical-trial","attrs":{"text":"NCT04909996","term_id":"NCT04909996"}}NCT04909996) and a complementary in vitro study on its activity against different respiratory viruses are reported. In the RCT, 57 patients were randomized (1:1:1) to receive STX three (STX-3) or five (STX-5) times/day plus standard therapy or standard therapy only (controls). Compared with controls, the log₁₀ load reduction in groups STX-3 and STX-5 was 1.02 (p = 0.14) and 0.18 (p = 0.80), respectively. These results were likely driven by outliers with extreme baseline viral loads. When considering subjects with baseline cycle threshold values of 20–30, STX-3 showed a significant (p = 0.016) 2.01 log₁₀ reduction. The proportion of subjects that turned negative by the end of treatment (day 5) was significantly higher in the STX-3 group than in controls, suggesting a shorter virus clearance time. STX was safe and well-tolerated. In the in vitro study, ≥99.9% reduction in titers against common respiratory viruses was observed. STX is a safe device with large virucidal spectrum and may reduce viral loads in mild COVID-19 patients.     

Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication

RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV.     

Burst Pressure Prediction of Subsea Supercritical CO2 Pipelines

To improve transportation efficiency, a supercritical CO₂ pipeline is the best choice for large-scale and long-distance transportation inshore and offshore. However, corrosion of the pipe wall will occur as a result of the presence of free water and other impurities present during CO₂ capture. Defects caused by corrosion can reduce pipe strength and result in pipe failure. In this paper, the burst pressure of subsea supercritical CO₂ pipelines under high pressure is investigated. First, a mechanical model of corroded CO₂ pipelines is established. Then, using the unified strength theory (UST), a new burst pressure equation for subsea supercritical CO₂ pipelines is derived. Next, analysis of the material’s intermediate principal stress parameters is conducted. Lastly, the accuracy of the burst pressure equation of subsea supercritical CO₂ pipelines is proven to meet the engineering requirement by experimental data. The results indicate that the parameter b of UST plays a significant role in determining burst pressure of pipelines. The study can provide a theoretical basis and reference for the design of subsea supercritical CO₂ pipelines.     

Innate and Adaptive Immune Responses in the Upper Respiratory Tract and the Infectivity of SARS-CoV-2

Increasing evidence shows the nasal epithelium to be the initial site of SARS-CoV-2 infection, and that early and effective immune responses in the upper respiratory tract (URT) limit and eliminate the infection in the URT, thereby preventing infection of the lower respiratory tract and the development of severe COVID-19. SARS-CoV-2 interferes with innate immunity signaling and evolves mutants that can reduce antibody-mediated immunity in the URT. Recent genetic and immunological advances in understanding innate immunity to SARS-CoV-2 in the URT, and the ability of prior infections as well as currently available injectable and potential intranasal COVID-19 vaccines to generate anamnestic adaptive immunity in the URT, are reviewed. It is suggested that the more detailed investigation of URT immune responses to all types of COVID-19 vaccines, and the development of safe and effective COVID-19 vaccines for intranasal administration, are important needs.     

New‐onset fulminant type 1 diabetes after severe acute respiratory syndrome coronavirus 2 vaccination: A case report

Fulminant type 1 diabetes is characterized by a rapid progression of insulin deficiency triggered by viral infection. Here, we report a case of a 45‐year‐old Japanese woman with fulminant type 1 diabetes that developed 8 days after receiving messenger ribonucleic acid vaccine against severe acute respiratory syndrome coronavirus 2. She had been healthy and had no symptoms suggestive of viral infection before the vaccination. Laboratory tests showed exhaustion of insulin secretion and negative results for islet autoantibodies. Human leukocyte antigen genotype analysis showed the DRB1*04:05 and DQB1*04:01 alleles. This is the first case report of new‐onset fulminant type 1 diabetes after severe acute respiratory syndrome coronavirus 2 vaccination, and suggests that a severe acute respiratory syndrome coronavirus 2 vaccine might trigger the onset of fulminant type 1 diabetes in susceptible individuals. However, a causal relationship remains to be identified, and further studies are required to determine the incidence of such cases.     

Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID‐19 context

Early initiation of breastfeeding, within 1 h of birth, is vital for the health of newborns and reduces morbidity and mortality. Secondary analysis of the 2016 Nepal Demographic and Health Survey (DHS) showed that early initiation of breastfeeding significantly reduced the risk of acute respiratory infection (ARI) in children under 2 years. Early initiation of breastfeeding requires maternal proximity. Separation of infant and mother inhibits early initiation of breastfeeding and increases the risk that infants will suffer from ARIs. However, during the COVID‐19 pandemic, guidance varied, with some recommending that infants and mothers with SARS‐CoV‐2 be isolated from one another. Nepal''s Ministry of Health and Population recommended nonseparation, but the adherence to this guidance was inconsistent. Maternal proximity, nonseparation and early initiation of breastfeeding should be promoted in all birthing facilities.