Abstract

Bovine viral diarrhea virus (BVDV) is one of the most important pathogens of cattle worldwide. BVDV-1 is widely distributed in Italy, while BVDV-2 has been detected occasionally. BVDV can be classified in two biotypes, cytopathic (CP) or noncytopathic (NCP). The characteristic of the virus is linked with the infection of a pregnant dam with a NCP strain: due to viral establishment before maturation of the fetal immune system the calf remains persistently infected (PI) and immunotolerant to the infecting BVDV strain. Thanks to their immunotolerance, PI animals represent a unique model to study the viral distribution and compartmentalization in absence of immunoresponse in vivo. In the present study, NGS sequencing was used to characterize the BVDV2 viral strain infecting a PI calf and to describe the viral quasispecies in tissues. Even if the consensus sequences obtained by all the samples were highly similar, quasispecies was described evaluating the presence and the frequency of variants among all the sequencing reads in each tissue. The results suggest a high heterogeneity of the infecting viral strain suggesting viral compartmentalization. The quasispecies analysis highlights the complex dynamics of viral population structure and can increase the knowledge about viral evolution in BVDV-2 persistently infected animals.

Highlights

  • Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus, family Flaviviridae

  • Since the infection occurs before the maturation of the fetal immune-system, viral proteins are considered as self antigens and the persistently infected (PI) calf remains immunotolerant to the BVDV strain, allowing the viral replication in all body compartments and the viral shedding during the entire animal life

  • The tree topology clearly shows that CN10.2015.821 strain belongs to the BVDV-2 clade (Fig. 1A)

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Summary

Introduction

Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus, family Flaviviridae. Since the infection occurs before the maturation of the fetal immune-system, viral proteins are considered as self antigens and the PI calf remains immunotolerant to the BVDV strain, allowing the viral replication in all body compartments and the viral shedding during the entire animal life. The high level of mutation rate can drive the virus to produce an heterogeneous population of closely related variants, known as mutant spectrum or quasispecies. This population diversity is known to be important in RNA virus evolution and survival, and many studies were conducted to explain viral quasispecies in RNA viruses[13,14]. These procedures are time-consuming and expensive, with biased outputs[36,37] making more difficult the study of viral population in considerable detail as they stop at consensus-level sequencing

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