Abstract
Genetic factors of resistance and predisposition to viral diseases explain a significant part of the clinical variability observed within host populations. Predisposition to viral diseases has been associated to MHC haplotypes and T cell immunity, but a growing repertoire of innate/intrinsic factors are implicated in the genetic determinism of the host susceptibility to viruses. In a long-term study of the genetics of host resistance to fish rhabdoviruses, we produced a collection of double-haploid rainbow trout clones showing a wide range of susceptibility to Viral Hemorrhagic Septicemia Virus (VHSV) waterborne infection. The susceptibility of fibroblastic cell lines derived from these clonal fish was fully consistent with the susceptibility of the parental fish clones. The mechanisms determining the host resistance therefore did not associate with specific host immunity, but rather with innate or intrinsic factors. One cell line was resistant to rhabdovirus infection due to the combination of an early interferon IFN induction - that was not observed in the susceptible cells - and of yet unknown factors that hamper the first steps of the viral cycle. The implication of IFN was well consistent with the wide range of resistance of this genetic background to VSHV and IHNV, to the birnavirus IPNV and the orthomyxovirus ISAV. Another cell line was even more refractory to the VHSV infection through different antiviral mechanisms. This collection of clonal fish and isogenic cell lines provides an interesting model to analyze the relative contribution of antiviral pathways to the resistance to different viruses.
Highlights
A fraction of individuals infected by viruses show clinical disease, and epidemiological evidences have established that the host genetic background plays an important role in the susceptibility to infections, explaining a significant part of the clinical variability observed within populations
We showed a remarkable correlation between the in vivo susceptibility to Viral Hemorrhagic Septicemia Virus (VHSV) infection of isogenic clones of rainbow trout and the susceptibility of the cell lines derived from these animals
Our results demonstrated that the variation of susceptibility to the virus depends on the genetic background and that the major pathways responsible for resistance are independent of the specific immune response
Summary
A fraction of individuals infected by viruses show clinical disease, and epidemiological evidences have established that the host genetic background plays an important role in the susceptibility to infections, explaining a significant part of the clinical variability observed within populations. Predisposition to viral diseases mirrors the resistance and contributes to the variability of their prevalence within populations Such predispositions may concern multiple infections when the mutation induces a general immune defect: typical genetic predispositions to multiple infections are due to global primary immunodeficiencies, which are generally rare and usually affect hematopoietic cells like in SCID and XLA [7,8]. In many cases a ‘‘major gene’’ or a ‘‘major locus’’ can be responsible for a significant part of the variability of complex traits including many phenotypes of variable susceptibility to infections Such major genes (or loci) have been identified for viral diseases using polymorphic markers in genome wide linkage analyses. The genetic determinism of viral diseases in human is still poorly known
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