- 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.
- A Novel Subunit Vaccine Based on Outer Capsid Proteins of Grass Carp Reovirus (GCRV) Provides Protective Immunity against GCRV Infection in Rare Minnow (Gobiocypris rarus). Mu C, Vakharia VN, Zhou Y, Jiang N, Liu W, Meng Y, Li Y, Xue M, Zhang J, Zeng L, Zhong Q, Fan Y. Pathogens. 2020 Nov 13;9(11):E945. doi: 10.3390/pathogens9110945. PMID: 33202780
- Effect of the Viral Hemorrhagic Septicemia Virus Nonvirion Protein on Translation via PERK-eIF2α Pathway. Kesterson SP, Ringiesn J, Vakharia VN, Shepherd BS, Leaman DW, Malathi K. Viruses. 2020 Apr 30;12(5):499. doi: 10.3390/v12050499. PMID: 32365817
- The Nucleoprotein and Phosphoprotein Are Major Determinants of the Virulence of Viral Hemorrhagic Septicemia Virus in Rainbow Trout. Vakharia VN, Li J, McKenney DG, Kurath G. J Virol. 2019 Aug 28;93(18):e00382-19. doi: 10.1128/JVI.00382-19. Print 2019 Sep 15. PMID: 31270224
- The glycoprotein, non-virion protein, and polymerase of viral hemorrhagic septicemia virus are not determinants of host-specific virulence in rainbow trout. Yusuff S, Kurath G, Kim MS, Tesfaye TM, Li J, McKenney DG, Vakharia VN. Virol J. 2019 Mar 7;16(1):31. doi: 10.1186/s12985-019-1139-3. PMID: 30845963
- Oral vaccination of Macrobrachium rosenbergii with baculovirus-expressed M. rosenbergii nodavirus (MrNV) capsid protein induces protective immunity against MrNV challenge. Citarasu T, Lelin C, Babu MM, Anand SB, Nathan AA, Vakharia VN. Fish Shellfish Immunol. 2019 Mar;86:1123-1129. doi: 10.1016/j.fsi.2018.12.010. Epub 2018 Dec 27. PMID: 30594582
- Newcastle Disease Virus Vectored Bivalent Vaccine against Virulent Infectious Bursal Disease and Newcastle Disease of Chickens. Dey S, Chellappa MM, Pathak DC, Gaikwad S, Yadav K, Ramakrishnan S, Vakharia VN. Vaccines (Basel). 2017 Sep 26;5(4):31. doi: 10.3390/vaccines5040031. PMID: 28954433
- 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
- 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