The full genome sequence of three strains of Jamestown Canyon virus and their pathogenesis in mice or monkeys

Abstract

Background: Jamestown Canyon virus (JCV), family Bunyaviridae, is a mosquito-borne pathogen endemic in the United States and Canada that can cause encephalitis in humans and is considered an emerging threat to public health. The virus is genetically similar to Inkoo virus circulating in Europe, suggesting that much of the northern hemisphere contains JCV or similar variants.

Results: We have completed the sequence of three isolates of JCV collected in geographically diverse locations over a 57 year time span. The nucleotide identity for the three strains is 90, 83, and 85% for the S, M, and L segments respectively whereas the percent identify for the predicted amino acid sequences of the N, NSS, M poly, GN, NSM, GC, and L proteins was 97, 91, 94, 98, 91, 94, and 97%, respectively. In Swiss Webster mice, each JCV isolate exhibits low neuroinvasiveness but high infectivity. Two of the three JCV isolates were highly neurovirulent after IC inoculation whereas one isolate, JCV/03/CT, exhibited low neurovirulence. In rhesus monkeys, JCV infection is accompanied by a low-titered viremia, lack of clinical disease, but a robust neutralizing antibody response.

Conclusions: The first complete sequence of JCV is reported for three separate isolates, and a relatively high level of amino acid sequence conservation was observed even for viruses isolated 57 years apart indicating that the virus is in relative evolutionary stasis. JCV is highly infectious for mice and monkeys, and these animals, especially mice, represent useful experimental hosts for further study.

Figure 1

Amino acid alignment of the predicted coding regions of the S segment. The consensus sequence consists of two or more sequences sharing the same amino acid residue at a given position and areas of no clear consensus are indicated with an "X".

Figure 2

Amino acid alignment of the predicted coding regions of the M segment. The consensus sequence consists of two or more sequences sharing the same amino acid residue at a given position and areas of no clear consensus are indicated with an "X".

Figure 3

Amino acid alignment of the predicted coding regions of the L segment. The consensus sequence consists of two or more sequences sharing the same amino acid residue at a given position and areas of no clear consensus are indicated with an "X".

Figure 4

Alignment of 3' (A) and 5' (B) non-coding regions of the S, M, and L genome segments (cDNA presented). For each segment the consensus sequence consists of two or more sequences sharing the same nucleotide at a given position and areas of no clear consensus are indicated with an "N", gaps in the sequences are represented by a dash (-). Underlined sequence indicates region known to be conserved amongst all orthobunyaviruses.

Figure 5

Growth kinetics of JCV isolates. Replication of JCV/61/CO-cl, JCV/03/CT-cl, and JCV/04/CT-cl in Vero (monkey kidney) or C6/36 (mosquito) cells infected at a MOI of 0.01.