Quasispecies composition and diversity do not reveal any predictors for chronic classical swine fever virus infection

Abstract

Classical swine fever (CSF) can run acute, chronic, and prenatal courses in both domestic pigs and wild boar. Although chronic infections are rare events, their epidemiological impact is very high due to the long-term shedding of virus. So far, little is known about the factors that influence disease course and outcome from either the host or virus's perspective. To elucidate the viral determinants, we analyzed the role of the viral populations for the development of chronic CSF virus (CSFV) infections. Three different animal trials that had led to both chronic and acute infections were chosen for a detailed analysis by deep sequencing. The three inocula represented sub-genogroups 2.1 and 2.3, and two viruses were wild-type CSFV, one derived from an infectious cDNA clone. These viruses and samples derived from acutely and chronically infected animals were subjected to next-generation sequencing. Subsequently, the derived full-length genomes were compared at both the consensus and the quasispecies level. At consensus level, no differences were observed between the parental viruses and the viruses obtained from chronically infected animals. Despite a considerable level of variability at the quasispecies level, no indications were found for any predictive pattern with regard to the chronicity of the CSFV infections. While there might be no direct marker for chronicity, moderate virulence of some CSFV strains in itself seems to be a crucial prerequisite for the establishment of long-term infections which does not need further genetic adaption. Thus, general host and virus factors need further investigation.

Strategy for efficient generation of numerous full-length cDNA clones of classical swine fever virus for haplotyping

“…The larger number of SNPs found in the latter study at higher frequencies, is most likely due to the Koslov strain being a wild-type virus, which has had a lot of time to evolve in its natural host, whereas vKos, as used in the present study, is a virus preparation derived from a unique cloned cDNA. Therefore, the rescued virus may be expected to consist of a less diverse quasispecies with respect to high frequency haplotypes than a highly virulent “field” isolate, as reported previously [ 28 ]. Over 79% of the SNPs observed in the clones, were detected in either the RNA-derived amplicons used in our study, in the serum of pigs infected with either vKos or vKos BAC clone variants, or in published CSFV sequences.…”

Classical Swine Fever—An Updated Review

“…Investigations into the role of quasispecies composition did not lead to the establishment of a clear correlation between variability and virulence [52]. There were also no predictors for different disease courses found [107]. …”

“…This, together with persistent infection, can play a role especially for affected wild boar populations [113,114,115], but also in endemically affected regions with constant virus circulation. Host rather than viral factors seem to play a role for the establishment of chronic infection [107]. …”

They are what you eat: Shaping of viral populations through nutrition and consequences for virulence

“…So, do viruses harboring higher genetic diversity initially fare better in establishing an infection and displaying virulent phenotypes? In studies with classical swine fever virus, higher genetic diversity correlated with virulence [23]; however, this conclusion has been challenged [24]. In other animal viruses, diversity increases precede the selection of virulent genomes [4].…”

“…In studies with classical swine fever virus, higher genetic diversity correlated with virulence [ 23 ]; however, this conclusion has been challenged [ 24 ]. In other animal viruses, diversity increases precede the selection of virulent genomes [ 4 ].…”