Abstract
Bovine viral diarrhea virus (BVDV), a Pestivirus in the family Flaviviridae, is an economically important pathogen of cattle worldwide. The primary propagators of the virus are immunotolerant persistently infected (PI) cattle, which shed large quantities of virus throughout life. Despite the absence of an acquired immunity against BVDV in these PI cattle there are strong indications of viral variability that are of clinical and epidemiological importance. In this study the variability of E2 and NS5B sequences in multiple body compartments of PI cattle were characterized using clonal sequencing. Phylogenetic analyses revealed that BVDV exists as a quasispecies within PI cattle. Viral variants were clustered by tissue compartment significantly more often than expected by chance alone with the central nervous system appearing to be a particularly important viral reservoir. We also found strong indications for a genetic bottleneck during vertical transmission from PI animals to their offspring. These quasispecies analyses within PI cattle exemplify the role of the PI host in viral propagation and highlight the complex dynamics of BVDV pathogenesis, transmission and evolution.
Highlights
Bovine viral diarrhea virus (BVDV) is a major production limiting disease of cattle due to the clinical signs following infection [1] and the associated economic consequences [2]
Our study focused on the N-terminal region of the ectodomain of the variable E2 [19] structural protein and the non-structural RNA-dependent RNA polymerase (RdRP) protein encoded by the relatively conserved NS5B [22]
A total of 10 persistently infected (PI) cattle were identified across five Western Canadian dairy herds (Table 1)
Summary
Bovine viral diarrhea virus (BVDV) is a major production limiting disease of cattle due to the clinical signs following infection [1] and the associated economic consequences [2]. Analysis of intrahost virus variability provides insight into localized evolutionary drivers and can reveal important determinants of viral pathogenesis that contribute to disease outcome. This virus population diversity is considered important in RNA virus evolution and survival and is attributed to the error prone genome replication by the RNA-dependent RNA polymerase (RdRP) [18]. Low frequency variants in the 5’UTR were detected in different tissues of a PI fetus [20] and, more recently, one study showed that genetic diversity increased more rapidly in PI animals than in multiple transient BVDV infections [21]. We describe the quasispecies diversity in the progeny of PI cattle, suggesting a genetic bottleneck following vertical transmission from PI dam to fetus
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