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Nervous necrosis virus (NNV) is a non-enveloped, icosahedral virus belonging to the genus Betanodavirus within the family Nodaviridae. It is the primary causative agent of Viral Encephalopathy and Retinopathy (VER), a highly contagious and lethal disease affecting more than 120 species of marine and freshwater fish globally (ICTV, 2023; PubMed, PMID: 31438568). The NNV genome is bipartite, consisting of two segments of positive-sense single-stranded RNA: RNA1, which encodes the RNA-dependent RNA polymerase (RdRp), and RNA2, which encodes the capsid protein (NCBI, 2022). The virus exhibits a strong tropism for the central nervous system, causing extensive vacuolation and necrosis in the brain and retina, which leads to abnormal swimming behavior and high mortality, particularly in larval and juvenile stages (ScienceDirect, 2021). Current therapeutic interventions are primarily focused on preventive measures, including the development of inactivated, subunit, and DNA vaccines targeting the capsid protein to elicit neutralizing antibodies. Additionally, experimental approaches such as RNA interference (RNAi) and the use of antimicrobial peptides like Epinecidin-1 are being explored to inhibit viral replication and entry (PubMed, PMID: 33572345).
Vaccines work by inducing the production of neutralizing antibodies that target the viral capsid protein, thereby preventing the virus from attaching to and entering host cells. Experimental RNA interference (RNAi) strategies utilize small interfering RNAs (siRNAs) to specifically degrade viral RNA1 or RNA2 segments, effectively blocking viral protein synthesis and genome replication within the host.
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