- Viral pathogenesis of fish rhabdoviruses
- Development of novel vaccines for economically important fish pathogens
My laboratory is studying the molecular biology of economically important fish viruses and focuses on viral pathogenesis and development of novel vaccines.
Current research in my laboratory has focused on two fish rhabdoviruses - infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), which are members of the genus Novirhabdovirus of the Rhabdoviridae family. Their genome is composed of approximately 11-kb of single-stranded RNA, which contains six genes that are located along the genome in the 3' to 5' order: 3'-N-P-M-G-NV-L-5', nucleocapsid protein (N), polymerase-associated phosphoprotein (P), matrix protein (M), surface glycoprotein (G), a unique non-virion protein (NV) and virus polymerase (L). IHNV and VHSV infect a number of fresh and saltwater fish worldwide and cause a highly contagious disease. Recently a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. We established the reverse genetics systems for both IHNV and VHSV whereby infectious rhabdovirus can be recovered entirely from cDNA clones. Using the reverse genetics approach, we are investigating the function of viral proteins in virulence, host adaptation, pathogenesis, and creating attenuated viruses with vaccine potential against other fish pathogens.
Nervous necrosis virus (NNV) and infectious pancreatic necrosis virus (IPNV) are pathogens of economic importance to the aquaculture industry. NNV causes viral encephalopathy and retinopathy in more than 30 species of marine warm-water and cold-water fish, whereas IPNV causes pancreatic necrosis disease in salmon and trout species. We are particularly interested in developing oral vaccines for these pathogens which could be suited to large-scale aquaculture operations. To this end, we have expressed the major host-protective genes of these viruses in suitable expression systems and seek to develop virus-like particles (VLPs) based vaccines that could be fed orally to fish.
Dr. Vakharia's research has led to the creation of a spin-off company, VakSea. Click here to see more.
1. Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription. Ke Q, Weaver W, Pore A, Gorgoglione B, Wildschutte JH, Xiao P, Shepherd BS, Spear A, Malathi K, Stepien CA, Vakharia VN, Leaman DW. J Virol. 2017 Sep 12;91(19). pii: e00279-17. doi: 10.1128/JVI.00279-17. Print 2017 Oct 1. PMID: 28747493 [PubMed - in process]
2. Crystal structure of an orthomyxovirus matrix protein reveals mechanisms for self-polymerization and membrane association. Zhang W, Zheng W, Toh Y, Betancourt-Solis MA, Tu J, Fan Y, Vakharia VN, Liu J, McNew JA, Jin M, Tao YJ. Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8550-8555. doi: 10.1073/pnas.1701747114. Epub 2017 Jul 24. PMID: 28739952 [PubMed - in process]
3. Molecular characterization of infectious pancreatic necrosis virus strains isolated from the three types of salmonids farmed in Chile. Manríquez RA, Vera T, Villalba MV, Mancilla A, Vakharia VN, Yañez AJ, Cárcamo JG. Virol J. 2017 Jan 31;14(1):17. doi: 10.1186/s12985-017-0684-x. PMID: 28143585 [PubMed - indexed for MEDLINE] Free PMC Article
4. Phylogenetic analysis of the glycoprotein gene of viral hemorrhagic septicemia virus from Iranian trout farms points towards a common European origin. Ghorani M, Adel M, Dadar M, Langeroudi AG, Kamyabi R, Vakharia VN, Einer-Jensen K. Vet Microbiol. 2016 Apr 15;186:97-101. doi: 10.1016/j.vetmic.2016.02.019. Epub 2016 Feb 26. PMID: 27016763 [PubMed - indexed for MEDLINE]
5. Identification and Characterization of MicroRNAs in Snakehead Fish Cell Line upon Snakehead Fish Vesiculovirus Infection. Liu X, Tu J, Yuan J, Liu X, Zhao L, Dawar FU, Khattak MN, Hegazy AM, Chen N, Vakharia VN, Lin L. Int J Mol Sci. 2016 Jan 26;17(2). pii: E154. doi: 10.3390/ijms17020154. PMID: 26821019 [PubMed - indexed for MEDLINE] Free PMC Article
6. Protective and immunogenic effects of Escherichia coli-expressed infectious pancreatic necrosis virus (IPNV) VP2-VP3 fusion protein in rainbow trout. Dadar M, Memari HR, Vakharia VN, Peyghan R, Shapouri MS, Mohammadian T, Hasanzadeh R, Ghasemi M. Fish Shellfish Immunol. 2015 Nov;47(1):390-6. doi: 10.1016/j.fsi.2015.09.007. Epub 2015 Sep 8. PMID: 26362208 [PubMed - indexed for MEDLINE]
7. Specific nucleotides at the 3'-terminal promoter of viral hemorrhagic septicemia virus are important for virulence in vitro and in vivo. Kim SH, Guo TC, Vakharia VN, Evensen Ø. Virology. 2015 Feb;476:226-32. doi: 10.1016/j.virol.2014.12.003. Epub 2014 Dec 30. PMID: 25553518 [PubMed - indexed for MEDLINE] Free Article
8. Interchange of L polymerase protein between two strains of viral hemorrhagic septicemia virus (VHSV) genotype IV alters temperature sensitivities in vitro. Kim SH, Yusuff S, Vakharia VN, Evensen Ø. Virus Res. 2015 Jan 2;195:203-6. doi: 10.1016/j.virusres.2014.10.013. Epub 2014 Oct 18. PMID: 25456404 [PubMed - indexed for MEDLINE]