Mapping of putative virulence motifs on infectious salmon anemia virus surface glycoprotein genes

Abstract

Infectious salmon anemia virus (ISAV) is classified in the genusIsavirus of the family Orthomyxoviridae. Although virulence variation of ISAV can be demonstrated experimentally in fish, virus strain identification is ambiguous because the correlates of pathogenicity and/or antigenicity of ISAV are not well defined. Thirteen ISAV isolates characterized for their ability to kill fish were used to search for markers of virulence on the virus surface glycoprotein genes; haemagglutinin-esterase (HE) and fusion (F) protein genes. A single amino acid change N 164 D in the putative globular head of the HE protein, and a deletion/insertion of ¡13 aa with the presence of a specific motif 352 FNT 354 in the highly polymorphic region spanning residues 337 V to M 372 in the HE protein stalk, in combination with a specific motif 265 YP 266 very close to the trypsin-cleavage site 267 RA/G 268 of the precursor F 0 protein were correlated with reduced cytopathogenicity and reduced virulence for Atlantic salmon. Phylogenetic analysis suggests that the original ancestral ISAV was virulent. The virulence of the North American genotype has not changed much, whereas the European genotype evolved into two genogroups, the real-European genogroup that is still virulent and the European-in-North America genogroup, which is of lower virulence. A novel phylogenetic software program, BACKTRACK, estimated that the North American and European genotypes diverged between 1879 and 1891, whereas the European-in-North America genogroup diverged from the real-European genogroup between 1976 and 1988. This direction of evolution supports insertion of specific motifs in the HE protein, resulting in ISAV attenuation.

Bioinformatic Analysis of the Genome of Infectious Salmon Anemia Virus Associated with Outbreaks with High Mortality in Chile

“…It has been suggested that the diversity of HPR sequences provides antigenic variability (56). HPR was proposed as a virulence marker, with the most virulent strains containing HPR4 (36,37,50,51), but some authors do not agree with that conclusion (65). Although every HPR in Chile has been identified, the most abundant is the genotype 7b, which originates from Norway (35).…”

First field evidence of the evolution from a non-virulent HPR0 to a virulent HPR-deleted infectious salmon anaemia virus

“…Differences in virulence among ISAV strains have been described in several studies [11][12][13][14]. Putatively uncultivable non-virulent ISAV variants (ISAV-HPR0) are characterized by an HE protein carrying a full-length highly polymorphic region (HPR) composed of at least 35 amino acids just upstream of the transmembrane domain [15][16][17][18][19].…”

Genetic markers of the immune response of Atlantic salmon (Salmo salar) to infectious salmon anemia virus (ISAV)

“…This isolate is also reported as HPR21 [22]. The titer was determined according to the SpearmaneKärber method [24] and the lysate was frozen until the challenge.…”

“…This would permit a primary testing of vaccine formulations, and only the most promising formulations would be advanced to full fish challenge models. The 32 K salmonid cDNA microarray developed by the consortium for Genomics Research on All Salmonids Project (cGRASP) (Gene Expression Omnibus (GEO)-GPL8904) was used to identify genes that were differentially expressed in head-kidneys of Atlantic salmon during the course of an infection with a virulent ISAV NA-HPR4 isolate (also referred as HPR21 in Kibenge et al (2007)) [22]. This isolate was previously shown to cause cumulative mortalities of 92% following an intra-peritoneal (IP) injection in a controlled environment [10].…”