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

Abstract

BackgroundJamestown 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.ResultsWe 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.ConclusionsThe 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.

Jamestown Canyon virus in Massachusetts: clinical case series and vector screening

“…Similarly, we did not detect JCV by RNA sequencing from acute serum and CSF from a third patient (Piantadosi et al, in preparation). While these were residual samples that may have been degraded by freeze/thaw cycles, our findings are consistent with prior results; JCV has never been isolated from human samples, and one study demonstrated no detectable viremia in experimentally infected rhesus macaques, despite seroconversion [34]. In general for orthobunyaviruses, it has been challenging to grow virus [35] or detect viral RNA in human samples; the few exceptions to this have included the detection of RNA from LACV in brain tissue [36], Oropouche virus in leukocytes [37], and Cache Valley virus in the CSF of an immunocompromised patient [38].…”

A Recombinant Chimeric La Crosse Virus Expressing the Surface Glycoproteins of Jamestown Canyon Virus Is Immunogenic and Protective against Challenge with either Parental Virus in Mice or Monkeys

“…We have previously demonstrated that JCV infection generates a neutralizing antibody response that also efficiently neutralizes both LACV and TAHV viruses (3,4). In the current study, we found that immunization with rJCV/LACV protected mice against lethal challenge with JCV, LACV, or TAHV.…”

“…JCV used in this study was a biological clone of the prototype strain 61V2235 (JCV/61/CO-cl) and previously sequenced and characterized (4). The recombinant LACV (rLACV) was generated from cDNA sequence of LACV strain 78 V 13193 (LACV/78/NC-cl) and was previously sequenced and characterized (5).…”

Throw out the Map: Neuropathogenesis of the Globally Expanding California Serogroup of Orthobunyaviruses

“…Interestingly, similar patterns of pathogenicity are observed in weanling mice inoculated with the CSG viruses known to cause human disease. Weanling mice are susceptible to disease from CEV, JCV, and INKV following IC or IN inoculation, but not following IP inoculation, indicating these viruses are neurovirulent, but not neuroinvasive, in mice [3,21,165]. LACV, SSHV, and TAHV all cause neuroinvasive disease in weanling mice following IP inoculation.…”

“…In experimental infections of rhesus monkeys inoculated subcutaneously or intramuscularly with LACV, TAHV, or JCV, none of the monkeys developed disease [125,165,168]. However, nearly all monkeys developed high neutralizing antibody titers, indicating they were productively infected [125,165,168].…”