Amino acidic substitutions in the polymerase N-terminal region of a reassortant betanodavirus strain causing poor adaptation to temperature increase

Abstract

Nervous necrosis virus (NNV), Genus Betanodavirus , is the causative agent of viral encephalopathy and retinopathy (VER), a neuropathological disease that causes fish mortalities worldwide. The NNV genome is composed of two single-stranded RNA molecules, RNA1 and RNA2, encoding the RNA polymerase and the coat protein, respectively. Betanodaviruses are classified into four genotypes: red-spotted grouper nervous necrosis virus (RGNNV), striped jack nervous necrosis virus (SJNNV), barfin flounder nervous necrosis virus (BFNNV) and tiger puffer nervous necrosis virus (TPNNV). In Southern Europe the presence of RGNNV, SJNNV and their natural reassortants (in both RNA1/RNA2 forms: RGNNV/SJNNV and SJNNV/RGNNV) has been reported. Pathology caused by these genotypes is closely linked to water temperature and the RNA1 segment encoding amino acids 1–445 has been postulated to regulate viral adaptation to temperature. Reassortants isolated from sole (RGNNV/SJNNV) show 6 substitutions in this region when compared with the RGNNV genotype (positions 41, 48, 218, 223, 238 and 289). We have demonstrated that change of these positions to those present in the RGNNV genotype cause low and delayed replication in vitro when compared with that of the wild type strain at 25 and 30 °C. The experimental infections confirmed the impact of the mutations on viral replication because at 25 °C the viral load and the mortality were significantly lower in fish infected with the mutant than in those challenged with the non-mutated virus. It was not possible to challenge fish at 30 °C because of the scarce tolerance of sole to this temperature.

Betanodavirus and VER Disease: A 30-year Research Review

“…The temperature sensitivity of betanodaviruses seems to be regulated by RNA1 [35,151] and more specifically by the region encoding the amino acid residues 1-445 [151]. Experiments performed with a recombinant strain harboring six point mutations in this region confirmed its role in viral thermotolerance, and pointed to position 223 as a putative responsible for temperature regulation [36]. This study, however, showed that genomic regions other than 1-445 may be involved in NNV thermotolerance.…”

Characterization of Novel Aptamers Specifically Directed to Red-Spotted Grouper Nervous Necrosis Virus (RGNNV)-Infected Cells for Mediating Targeted siRNA Delivery

“…Nervous necrosis virus (NNV), one of the most devastating marine viruses, typically causes viral nervous necrosis (VNN) or viral encephalopathy and retinopathy (VER) in the larvae and juveniles of marine and freshwater fish (Souto et al, 2019). In recent years, NNV has spread to more than 50 fish species around Europe, Australia, Martinique, North America, Tahiti, and Asia (Liu et al, 2012;Doan et al, 2017).…”

Characterization of the prion protein gene in axis deer (Axis axis) and implications for susceptibility to chronic wasting disease

“…Definitive evidence such as a positive ELISA or IHC test or a protein misfolding cyclic amplification (PMCA) study of axis deer PrP C is needed to conclusively demonstrate axis deer are capable of contracting CWD. However, this research in combination with other work indicating a wider range of susceptible species than previously known [ 13 , 19 ], suggests axis deer in Texas and Hawaii may be susceptible to CWD, and should be managed as an at-risk species for CWD through the implementation of more formalized CWD surveillance. The proactive establishment of a CWD testing programme in axis deer wherever CWD has been detected in other species may be justified.…”

“…However, the highly conserved nature of PRNP within and among taxa may contribute to this finding [ 1 , 26 ]. Furthermore, a previous assessment of PRNP found PRNP to be monomorphic in roe deer ( Capreolus capreolus , n = 297) and fallow deer (n = 66) [ 19 ].…”

“…Phylogenetic analyses and challenge studies indicate species beyond Cervidae, including pronghorn ( Antilocapra americana ), bighorn sheep ( Ovis canadensis ), mountain goat ( Oreamnos americanus ), and squirrel monkeys ( Saimiri sciureus ) may be susceptible to infection by the CWD prion and CWD susceptibility is not monophyletic within Cervidae [ 13 , 16 , 17 ]. The various lines of evidence suggest many, if not all, members of Cervidae are likely susceptible to CWD, including those that naturally occur outside of North America [ 18 , 19 ].…”