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International Journal of Molecular... May 2023Feline leukemia virus (FeLV) is one of the most prevalent infectious diseases in domestic cats. Although different commercial vaccines are available, none of them...
Feline leukemia virus (FeLV) is one of the most prevalent infectious diseases in domestic cats. Although different commercial vaccines are available, none of them provides full protection. Thus, efforts to design a more efficient vaccine are needed. Our group has successfully engineered HIV-1 Gag-based VLPs that induce a potent and functional immune response against the HIV-1 transmembrane protein gp41. Here, we propose to use this concept to generate FeLV-Gag-based VLPs as a novel vaccine strategy against this retrovirus. By analogy to our HIV-1 platform, a fragment of the FeLV transmembrane p15E protein was exposed on FeLV-Gag-based VLPs. After optimization of Gag sequences, the immunogenicity of the selected candidates was evaluated in C57BL/6 and BALB/c mice, showing strong cellular and humoral responses to Gag but failing to generate anti-p15E antibodies. Altogether, this study not only tests the versatility of the enveloped VLP-based vaccine platform but also sheds light on FeLV vaccine research.
Topics: Mice; Animals; Cats; Leukemia Virus, Feline; Vaccines, Virus-Like Particle; Mice, Inbred C57BL; HIV-1; Retroviridae; HIV Envelope Protein gp41
PubMed: 37240371
DOI: 10.3390/ijms24109025 -
Journal of Cellular and Molecular... Dec 2022We are committed to finding host targets for influenza A therapeutics. The nucleoprotein (NP) plays an important role in influenza A virus replication and is an...
We are committed to finding host targets for influenza A therapeutics. The nucleoprotein (NP) plays an important role in influenza A virus replication and is an indispensable part of viral transcription and replication. Exploring endogenous substances that can modulate NP is critical for finding host targets. MicroRNAs (miRNAs, miR) are a novel class of powerful, endogenous gene expression regulators. Herein, we used miRanda to analyse the base complementarity between the NP gene and the 14 host miRNAs reported previously by us. MiRanda predicted that miR-431-5p, miR-744-3p and miR-205-5p could complement the NP gene. To understand the effect of these miRNAs on NP expression, we co-transfected 293 T cells with NP gene sequence containing above miRNAs binding site or full sequence of NP gene (transfected into pmirGlo or pcDNA3.1 vectors, respectively), and mimics of miR-205-5p, miR-431-5p and miR-744-3p. Dual luciferase reporter gene or Western blotting assays confirmed that miR-205-5p and miR-431-5p inhibit NP expression by binding with the miRNA binding site of NP gene. Further, we infected Mouse Lung Epithelial (MLE-12) cells overexpressing miR-205-5p and miR-431-5p with influenza A virus and performed Western blotting to examine NP expression. We found that NP expression was significantly reduced in MLE-12 cells overexpressing miR-205-5p during influenza A infection. The miR-205-5p overexpression-induced inhibition of influenza A replication could be attributed to the inhibition of NP expression. Further, we administered oseltamivir and Jinchai Antiviral Capsules (JC, an anti-influenza Chinese medicine) to influenza A virus-infected MLE-12 cells and mice. We found that miR-205-5p was significantly decreased increased in infected cells and lung tissues, and oseltamivir and JC could up-regulate miR-205-5p. In conclusion, we provide new evidence that miR-205-5p plays a role in regulating viral NP protein expression in combating influenza A and may be a potential target for influenza A therapy.
Topics: Animals; Mice; Binding Sites; Influenza A virus; MicroRNAs; Oseltamivir; Orthomyxoviridae Infections
PubMed: 36403222
DOI: 10.1111/jcmm.17615 -
International Journal of Molecular... Apr 2024CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both... (Review)
Review
CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases.
Topics: Chemokine CX3CL1; Humans; Virus Diseases; Animals; COVID-19; SARS-CoV-2; Microglia; CX3C Chemokine Receptor 1
PubMed: 38674036
DOI: 10.3390/ijms25084451 -
Vaccine Jun 2023Although mumps vaccination has been routine in Canada for decades, mumps cases and outbreaks continue to occur periodically. Mumps surveillance, including monitoring of...
Although mumps vaccination has been routine in Canada for decades, mumps cases and outbreaks continue to occur periodically. Mumps surveillance, including monitoring of the mumps virus genotype associated with disease activity, is important to document baseline activity and to advance further research into vaccine effectiveness. Here we describe a detailed analysis of mumps cases that have been detected in Canada from 2002 to 2020, with a focus on the mumps molecular epidemiology. In total, 7395 cases of mumps were reported to the surveillance system, with outbreaks occurring in the years 2007, 2010 and 2016 to 2018. Adolescents and young adults aged 15 to 29 years had the highest risk of being a case (rate ratios ranging from 1.50 to 2.29), compared to adults aged 30 to 39. Genotypes of mumps viruses were determined in 3225 specimens. Genotype G was predominantly detected (96% of genotyped specimens) and was first reported in 2005. Other genotypes were more likely to be detected in cases that also reported travel (or were linked to imported cases) than the cases with genotype G detected (p < 0.0001). The genotype G viruses had little sequence diversity in the 316 nucleotide window used for genotyping (the small hydrophobic protein gene) and mainly belonged to a single phylogenetic lineage that included the MuVi/Sheffield.GBR/1.05 reference sequence. The analysis of over ten years of data has demonstrated that mumps genotype G, specifically belonging to a single lineage, the Sheffield lineage, is the endemically circulating virus in Canada. This lineage is seen also in other countries using the genotype A vaccine. Mumps remains endemic despite high MMR vaccination coverage which has been sufficient to eliminate circulation of measles and rubella in Canada, raising the hypothesis of the evolution towards a vaccine escape mumps virus.
Topics: Adolescent; Young Adult; Humans; Mumps; Phylogeny; Measles-Mumps-Rubella Vaccine; Mumps virus; Canada; Disease Outbreaks
PubMed: 37169652
DOI: 10.1016/j.vaccine.2023.04.078 -
Viruses Oct 2020Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the... (Review)
Review
Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or gene fragments, insertion of foreign genes, and swapping genes between PRRSV strains or between PRRSV and other members of the family. In this review, we describe the approaches to construct an infectious cDNA for PRRSV and the ten major applications of these infectious clones to study virus biology and virus-host interaction, and to design a new generation of vaccines with improved levels of safety and efficacy.
Topics: Animals; DNA, Complementary; Genome, Viral; Host Microbial Interactions; Mutagenesis, Site-Directed; Porcine Reproductive and Respiratory Syndrome; Porcine respiratory and reproductive syndrome virus; Reverse Genetics; Swine; Virus Replication
PubMed: 33142752
DOI: 10.3390/v12111245 -
Current HIV/AIDS Reports Dec 2022Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection that remains an important cause of morbidity and mortality in people living with HIV... (Review)
Review
PURPOSE OF REVIEW
Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection that remains an important cause of morbidity and mortality in people living with HIV (PLWH). Immune checkpoint molecules are negative regulators of the immune response that have been targeted as a strategy to bolster anti-viral immunity in PML, with varied outcomes reported. While initiation and optimization of antiretroviral therapy remains the standard of care in HIV-related PML, the specific opportunities and risks for checkpoint blockade in these cases should be explored.
RECENT FINDINGS
As of April 15, 2022, only 5 of the 53 total published cases of PML treated with checkpoint blockade had underlying HIV infection; four of these had a favorable outcome. The risk of promoting immune reconstitution inflammatory syndrome is a major concern and underscores the importance of patient selection and monitoring. Checkpoint blockade warrants further exploration as a potentially promising option for treatment escalation in HIV-related PML.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; HIV Infections; JC Virus; Immune Reconstitution Inflammatory Syndrome; Antiviral Agents
PubMed: 36181625
DOI: 10.1007/s11904-022-00626-w -
International Journal of Molecular... Sep 2023Up to 50% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) infection, and the surface protein of HBV is essential for the progression of...
Up to 50% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) infection, and the surface protein of HBV is essential for the progression of HBV-related HCC. The expression of large HBV surface antigen (LHB) is presented in HBV-associated HCC tissues and is significantly associated with the development of HCC. Gene set enrichment analysis revealed that LHB overexpression regulates the cell cycle process. Excess LHB in HCC cells induced chronic endoplasmic reticulum (ER) stress and was significantly correlated with tumor growth in vivo. Cell cycle analysis showed that cell cycle progression from G1 to S phase was greatly enhanced in vitro. We identified intensive crosstalk between ER stress and cell cycle progression in HCC. As an important regulator of the G1/S checkpoint, p27 was transcriptionally upregulated by transcription factors ATF4 and XBP1s, downstream of the unfolded protein response pathway. Moreover, LHB-induced ER stress promoted internal ribosome-entry-site-mediated selective translation of p27, and E3 ubiquitin ligase HRD1-mediated p27 ubiquitination and degradation. Ultimately, the decrease in p27 protein levels reduced G1/S arrest and promoted the progress of HCC by regulating the cell cycle.
Topics: Humans; Carcinoma, Hepatocellular; Cyclin-Dependent Kinase Inhibitor p27; Hepatitis B; Hepatitis B virus; Immunologic Factors; Liver Neoplasms; Membrane Proteins; Unfolded Protein Response
PubMed: 37762128
DOI: 10.3390/ijms241813825 -
Viruses May 2023Reactivation of JC and BK polyomaviruses during immunosuppression can lead to adverse clinical outcomes. In renal transplant recipients, BKV-associated nephropathy can...
BACKGROUND
Reactivation of JC and BK polyomaviruses during immunosuppression can lead to adverse clinical outcomes. In renal transplant recipients, BKV-associated nephropathy can result in graft loss, while in patients with autoimmune disorders, prolonged immunomodulatory drug use can cause rare onset of progressive multifocal leukoencephalopathy due to JCV reactivation. In such patients, accurate BK and JC viral load determinations by molecular technologies are important for diagnosis and clinical management; however, comparability across centres requires effective standardisation of diagnostic molecular detection systems. In October 2015, the WHO Expert Committee for Biological Standardisation (ECBS) established the 1st WHO International Standards (ISs) for use as primary-order calibrants for BKV and JCV nucleic acid detection. Two multi-centre collaborative studies confirmed their utility in harmonising agreement across the wide range of BKV and JCV assays, respectively. Previous Illumina-based deep sequence analysis of these standards, however, identified deletions in different regions, including the large T-antigen coding region. Hence, further detailed characterization was warranted.
METHODS
Comprehensive sequence characterisation of each preparation using short- and long-read next-generation sequencing technologies was performed with additional corroborative independent digital PCR (dPCR) determinations. Potential error rates associated with long-read sequencing were minimised by applying rolling circle amplification (RCA) protocols for viral DNA (circular dsDNA), generating a full validation of sequence identity and composition and delineating the integrity of full-length BK and JC genomes.
RESULTS
The analysed genomes displayed subpopulations frequently characterised by complex gene re-arrangements, duplications and deletions.
CONCLUSIONS
Despite the recognition of such polymorphisms using high-resolution sequencing methodologies, the ability of these reference materials to act to enhance assay harmonisation did not appear significantly impacted, based on data generated by the 2015 WHO collaborative studies, but highlights cautionary aspects of IS generation and commutability for clinical molecular diagnostic application.
Topics: Humans; JC Virus; BK Virus; Polyomavirus Infections; Leukoencephalopathy, Progressive Multifocal; DNA, Viral; World Health Organization; Tumor Virus Infections
PubMed: 37376589
DOI: 10.3390/v15061289 -
AIDS (London, England) Oct 2023Over 480 000 Ukrainian refugees have arrived in the Czech Republic since the Russian invasion of Ukraine in 2022, including over 500 people with HIV. This study...
OBJECTIVE
Over 480 000 Ukrainian refugees have arrived in the Czech Republic since the Russian invasion of Ukraine in 2022, including over 500 people with HIV. This study describes the demographics, characteristics, and management of Ukrainian refugees with HIV in the Czech Republic.
DESIGN
Retrospective, observational, noninterventional study.
METHODS
Ukrainian nationals registering at HIV centers in the Czech Republic with war refugee status were included. Data were collected from medical records between 1 March and 31 July 2022. The study was registered with the Czech State Institute for Drug Control, ID number 2301200000.
RESULTS
Four hundred and eighty-two patients were included in the study. Most patients were female (69.5%; n = 335/482) with well-controlled HIV. The median [interquartile range] CD4 + cell count was 597 [397] cells/μl of blood, and 79.3% ( n = 361/455) of patients had HIV RNA <40 copies/ml. Coinfections of hepatitis C virus, hepatitis B virus, and/or tuberculosis were reported for 17.4% ( n = 78/449), 9% ( n = 40/446) and 1.3% ( n = 6/446) of patients, respectively. In Ukraine, 85.7% ( n = 384/448) of patients had been receiving an integrase strand transfer inhibitor-based regimen and most (69.7%; n = 310/445) did not switch therapy upon arrival in the Czech Republic.
CONCLUSION
Migration from Ukraine is changing the characteristics of HIV epidemiology in the Czech Republic. Ukrainian refugees with HIV have been provided with a high standard of medical care in the Czech Republic. Improved coordination between medical services within the Czech Republic and between countries in the European Union is necessary to optimize patient care.
Topics: Humans; Female; Male; Czech Republic; Refugees; Retrospective Studies; HIV Infections; Tuberculosis
PubMed: 37352491
DOI: 10.1097/QAD.0000000000003633 -
Viruses Apr 2023Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular...
Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011-2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; Japan; JC Virus; Polymerase Chain Reaction; DNA, Viral
PubMed: 37112948
DOI: 10.3390/v15040968