Background: West Nile Virus (WNV) is a flavivirus that requires an efficient humoral and cellular host response for the control of neuroinvasive infection. We previously reported the existence of six alternative open reading frame proteins in WNV genome, one of which entitled WARF4 is exclusively restricted to the lineage I of the virus. WARF4 is able to elicit antibodies in WNV infected horses; however, there was no direct experimental proof of the existence of this novel protein. The purpose of this study was to demonstrate the in vitro production of WARF4 protein following WNV infection of cultured VERO cells and its immunity in WNV infected individuals.
Results: We produced a monoclonal antibody against WARF4 protein (MAb 3A12) which detected the novel protein in WNV lineage I-infected, cultured VERO cells while it did not react with WNV lineage II infected cells. MAb 3A12 specificity to WARF4 protein was confirmed by its reactivity to only one peptide among four analyzed that cover the full WARF4 amino acids sequence. In addition, WARF4 protein was expressed in the late phase of WNV lineage I infection. Western blotting and bioinformatics analyses strongly suggest that the protein could be translated by programmed -1 ribosomal frameshifting process. Since WARF4 is embedded in the NS4B gene, we rename this novel protein N-NS4B/WARF4. Furthermore, serological analysis shows that N-NS4B/WARF4 is able to elicit antibodies in WNV infected individuals.
Conclusions: N-NS4B/WARF4 is the second Alternative Reading Frame (ARF) protein that has been demonstrated to be produced following WNV infection and might represent a novel tool for a better characterization of immune response in WNV infected individuals. Further serological as well as functional studies are required to characterize the function of the N-NS4B/WARF4 protein. Since the virus might actually make an extensive use of ARFs, it appears important to investigate the novel six ARF putative proteins of WNV.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574045 | PMC |
| http://dx.doi.org/10.1186/1743-422X-9-283 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exploiting venom toxins in paratransgenesis to prevent mosquito-borne disease.
Parasit Vectors
January 2025
Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing.
View Article and Find Full Text PDFA single-cell atlas of the Culex tarsalis midgut during West Nile virus infection.
PLoS Pathog
January 2025
Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
The mosquito midgut functions as a key interface between pathogen and vector. However, studies of midgut physiology and virus infection dynamics are scarce, and in Culex tarsalis-an extremely efficient vector of West Nile virus (WNV)-nonexistent. We performed single-cell RNA sequencing on Cx.
View Article and Find Full Text PDFDengue virus is particularly sensitive to interference with long-chain fatty acid elongation and desaturation.
J Biol Chem
January 2025
Institute of Virology, Philipps University Marburg, Marburg, Germany. Electronic address:
Orthoflaviviruses are emerging arthropod-borne pathogens whose replication cycle is tightly linked to host lipid metabolism. Previous lipidomic studies demonstrated that infection with the closely related hepatitis C virus (HCV) changes the fatty acid (FA) profile of several lipid classes. Lipids in HCV-infected cells had more very long-chain and desaturated FAs and viral replication relied on functional FA elongation and desaturation.
View Article and Find Full Text PDFA Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.
Viruses
January 2025
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami/UHealth, Miami, FL 33136, USA.
Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy.
View Article and Find Full Text PDFLatin America's Dengue Outbreak Poses a Global Health Threat.
Viruses
January 2025
Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 5508-900, Brazil.
Dengue fever, caused by the dengue virus (DENV), poses a significant global health challenge, particularly in tropical and subtropical regions. Recent increases in indigenous DENV cases in Europe are concerning, reflecting rising incidence linked to climate change and the spread of mosquitoes. These vectors thrive under environmental conditions like temperature and humidity, which are increasingly influenced by climate change.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!