Pathogenicity evaluation of twelve West Nile virus strains belonging to four lineages from five continents in a mouse model: discrimination between three pathogenicity categories

Abstract

Rodent models have been used extensively to study West Nile virus (WNV) infection because they develop severe neurological symptoms similar to those observed in human WNV neuroinvasive disease. Most of this research has focused on old lineage (L) 1 strains, while information about pathogenicity is lacking for the most recent L1 and L2 strains, as well as for newly defined lineages. In this study, 4-week-old Swiss mice were inoculated with a collection of 12 WNV isolates, comprising 10 old and recent L1 and L2 strains, the putative L6 strain from Malaysia and the proposed L7 strain Koutango (KOU). The intraperitoneal inoculation of 10-fold dilutions of each strain allowed the characterization of the isolates in terms of LD50, median survival times, ID50, replication in neural and extraneural tissues and antibody production. Based on these results, we classified the isolates in three groups: high virulence (all L1a strains, recent L2 strains and KOU), moderate virulence (B956 strain) and low virulence (Kunjin and Malaysian isolates). We determined that the inoculation of a single dose of 1000 p.f.u. would be sufficient to classify WNV strains by pathotype. We confirmed the enhanced virulence of the KOU strain with a high capacity to cause rapid systemic infection. We also corroborated that differences in pathogenicity among strains do not correlate with phylogenetic lineage or geographic origin, and confirmed that recent European and African WNV strains belonging to L1 and L2 are highly virulent and do not differ in their pathotype profile compared to the prototype NY99 strain.

First isolation of West Nile virus in Zambia from mosquitoes

“…The Zmq16m11 was in the same cluster as WNV South African isolates, HS101_08, SPU116/89 and SA93/01 (Botha et al., ; Mentoor et al., ). These WNV strains were originally isolated from human cases of WNV infection (SPU116/89 and SA93/01) and from a WNV‐infected horse (HS101_08) and all have been shown to be highly pathogenic in mouse models (Beasley, Li, Suderman, & Barrett, ; Pérez‐Ramírez et al., ; Venter et al., ). The differences in the amino acid sequences of coding proteins and nucleotide sequences of non‐coding regions between Zmq16m11 and South African strains are shown in Table .…”

The Role of Birds of Prey in West Nile Virus Epidemiology

“…Differences in WNV pathology in raptors likely arise from a combination of factors related to the host and the virus strain involved. Host factors are linked to genetic variation between species, but also within species in different populations, and even at the individual level [ 3 , 29 , 86 ]. On the other hand, virus factors, such as the presence of virulence determinants in the viral genome, also influence the outcome of the infection in each host [ 3 , 87 ].…”

“…Host factors are linked to genetic variation between species, but also within species in different populations, and even at the individual level [ 3 , 29 , 86 ]. On the other hand, virus factors, such as the presence of virulence determinants in the viral genome, also influence the outcome of the infection in each host [ 3 , 87 ]. Non-progressive, acute, or more prolonged course of disease will also partly affect the severity and distribution of lesions and viral antigen detection in different organs.…”

“…WNV is member of the genus Flavivirus of the family Flaviviridae . WNV strains are classified into at least 7 genetic lineages [ 1 , 2 ] with highly pathogenic isolates mainly belonging to lineage 1 (L1) and 2 (L2) strains [ 3 ]. It causes a febrile disease in humans and horses that in some cases progresses to fatal encephalitis.…”

Dynamics of Tissue-Specific CD8 + T Cell Responses during West Nile Virus Infection

“…WNV infection of mice recapitulates many aspects of viral pathogenesis observed in WNV-infected humans (10). Through the use of the murine model, several components of the innate and adaptive immune response have been found to control WNV replication, tissue tropism, and infection outcome.…”