Jamestown Canyon virus
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Jamestown Canyon encephalitis is an infectious disease caused by the Jamestown Canyon virus, an
orthobunyavirus ''Orthobunyavirus'' is a genus of the '' Peribunyaviridae'' family in the order ''Bunyavirales''. There are currently ~170 viruses recognised in this genus. These have been assembled into 103 species and 20 serogroups. The name ''Orthobunyavirus ...
of the California serogroup. It is mainly spread during the summer by different
mosquito Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning " gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "li ...
species in the United States and Canada. The virus is one of a group of mosquito-borne or arthropod-borne viruses, also called
arbovirus Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term ''arbovirus'' is a portmanteau word (''ar''thropod-''bo''rne ''virus''). ''Tibovirus'' (''ti''ck-''bo''rne ''virus'') is sometimes used to more sp ...
es, that can cause fever and meningitis or
meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
, mostly in adults. Jamestown Canyon virus disease is relatively rare; in the United States, the CDC found only 31 disease cases from 2000 to 2013, but it is likely under-recognized and probably
endemic Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found else ...
throughout most of the United States and parts of Canada.


Signs and symptoms

About 2 days to 2 weeks after the bite of an infected mosquito, disease symptoms of a nonspecific summertime illness with sore throat, runny nose and cough, followed by fever, headache, nausea and vomiting can develop. Many cases are asymptomatic, although the ratio of symptomatic to asymptomatic cases is unknown. Neuroinvasive disease occurs in two thirds of reported cases and is characterized by severe headache and neck stiffness as in meningitis or increasing lethargy and altered mental status up to coma as in
meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
. Roughly half of reported cases are hospitalized, but deaths from the virus are rare. No acquisition from a blood transfusion has been reported.


Virology

The Jamestown Canyon virus is an
orthobunyavirus ''Orthobunyavirus'' is a genus of the '' Peribunyaviridae'' family in the order ''Bunyavirales''. There are currently ~170 viruses recognised in this genus. These have been assembled into 103 species and 20 serogroups. The name ''Orthobunyavirus ...
and was first isolated in 1961 from Culiseta mosquitoes in
Jamestown, Colorado The historic Town of Jamestown is a Statutory Town in Boulder County, Colorado, United States. The population was 274 at the 2010 United States Census. It was named for James Smith, an early discoverer of gold.Aedes ''Aedes'' is a genus of mosquitoes originally found in tropical and subtropical zones, but now found on all continents except perhaps Antarctica. Some species have been spread by human activity: '' Aedes albopictus'', a particularly invasive sp ...
, Coquillettidia perturbans,
Culex ''Culex'' is a genus of mosquitoes, several species of which serve as vectors of one or more important diseases of birds, humans, and other animals. The diseases they vector include arbovirus infections such as West Nile virus, Japanese encep ...
, Culiseta and
Ochlerotatus ''Ochlerotatus'' is a genus of mosquito. Until 2000, it was ranked as a subgenus of ''Aedes'', but after Reinert's work, the clade was upgraded to the level of a genus. This change has resulted in the renaming of many subgenus species, and many a ...
species in northern states of the mainland US, in various mammals throughout mainland North America, and identified in humans throughout the United States.


Lifecycle

The virus is transmitted in saliva to a vertebrate host when an infected mosquito takes a blood meal. It thus cycles between mosquito and vertebrate amplifier hosts, mainly
white-tailed deer The white-tailed deer (''Odocoileus virginianus''), also known as the whitetail or Virginia deer, is a medium-sized deer native to North America, Central America, and South America as far south as Peru and Bolivia. It has also been introduced t ...
. In a study from Newfoundland, JCV was significantly associated with large mammals such as sheep, cattle and horses. In Michigan and Ontario moose and bison are believed to be the primary reservoir. The virus winters in mosquito eggs, which it reaches by
transovarial transmission Transovarial or transovarian transmission (transmission from parent to offspring via the ovaries) occurs in certain arthropod vectors as they transmit pathogens from parent to offspring. This process, used by a wide variety of parasites, is also kn ...
. The female mosquito lays eggs that carry the virus, and the offspring can transmit the virus to deer or ruminants and humans. Infected mosquitoes were found equally distributed throughout the state of Connecticut, irrespective of land use.


Molecular biology

The full
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
has been sequenced. The authors found a relatively high level of amino acid
sequence conservation In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ...
from viruses isolated 57 years apart "indicating that the virus is in relative evolutionary stasis". They also found JCV to be genetically similar to
Ingå Ingå (; fi, Inkoo) is a municipality of Finland. Ingå is located in the province of Southern Finland and is part of the Uusimaa region. The municipality has a population of () and covers an area of of which is water. The population density ...
virus in Northern Europe (Finland, Sweden), "suggesting that much of the northern hemisphere contains JCV or similar variants". The negative sense RNA genome is in three segments. The L segment encodes the L endonuclease (an RNA-dependent RNA polymerase enzyme) for genome replication and mRNA synthesis. The M segment encodes a polyprotein, further cleaved in the Gn and Gc surface glycoproteins for attachment and the NSm nonstructural protein that influences virulence. The S segment encodes the NSs protein for immune suppression and virulence, and the N structural nucleocapsid protein.


Diagnosis

The
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
considers a person with JCV infection laboratory-confirmed if: JCV isolated from or JCV-specific antigen or genomic sequences detected in tissue, blood, cerebrospinal fluid, or other body fluids; 2) equal or more than 4-fold change in JCV-specific
neutralizing antibody A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibod ...
titers between acute and convalescent samples; or 3) JCV or LACV
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
antibodies in serum with JCV-specific neutralizing antibodies equal or more than 4-fold higher than LACV-specific neutralizing antibody titers in the same specimen or a later specimen. JCV-antibody testing has only been available at the CDC and the
New York State Department of Health The New York State Department of Health (NYSDOH) is the department of the New York state government responsible for public health. It is headed by Health Commissioner Mary T. Bassett, who was appointed by Governor Hochul and confirmed by the S ...
. The CDC has used
plaque reduction neutralization test The plaque reduction neutralization test is used to quantify the titer of neutralizing antibody for a virus. The serum sample or solution of antibody to be tested is diluted and mixed with a viral suspension. This is incubated to allow the antibody ...
s to detect JCV neutralizing antibodies since 1995. The test is automatically done on all samples testing positive or equivocal for La Crosse Virus IgM antibodies by
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
. In 2010 CDC developed an ELISA also for JCV IgM . Similarly, the New York State Department of Health has performed JCV plaque reduction neutralization tests since 2000 on samples positive for California serogroup IgG antibodies. It does the latter by an
immunofluorescence assay Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...
. Prior to the 1990s, the only tests for California serogroup virus infections performed by most state diagnostic laboratories were
complement-fixation test The complement fixation test is an immunological medical test that can be used to detect the presence of either specific antibody or specific antigen in a patient's serum, based on whether complement fixation occurs. It was widely used to diagnose ...
and hemagglutination inhibition tests with La Crosse virus, but these failed to detect antibody to Jamestown Canyon virus.


Differential diagnosis

Besides La Crosse virus, other arboviruses producing similar disease in a similar geographic location include first and foremost
West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family '' Flaviviridae'', from the genus '' Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The v ...
, Powassan virus, Eastern equine encephalitis virus,
Saint Louis encephalitis Saint Louis encephalitis is a disease caused by the mosquito-borne Saint Louis encephalitis virus. Saint Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the family ''Flaviviridae''. This disease mainly affe ...
and
Western equine encephalitis virus The Western equine encephalomyelitis virus is the causative agent of relatively uncommon viral disease ''Western equine encephalomyelitis'' (WEE). An alphavirus of the family '' Togaviridae'', the WEE virus is an arbovirus (arthropod-borne vir ...
, the latter two not being reportable to CDC. For 2013, CDC reported that of 22 JCV disease cases, 15 (68%) were neuroinvasive, which is a slightly higher percentage than for West Nile virus (51%), but less common than for the other arboviruses, with La Crosse virus being 91%, Eastern equine encephalitis virus 100% and Powassan virus 80% neuroinvasive.


Treatment and prevention

No specific therapy exists for arboviral infections; treatment is limited to supportive care and managing complications, such as relieving increased intracranial pressure. Preventing and decreasing the morbidity from JCV disease depends on control of the mosquito vectors and personal protection to reduce mosquito bites. The NIAID reported in 2012, that it had constructed a candidate virus for a live attenuated virus vaccine.


Epidemiology

Since 2004, the disease must be reported to CDC (passive surveillance, ArboNET). JCV has been mostly reported in adults rather than in children ( median age 48 years versus 8 years), and is more likely to cause meningitis than encephalitis compared to illness caused by
La Crosse virus La Crosse encephalitis is an encephalitis caused by an arbovirus (the La Crosse virus) which has a mosquito vector ('' Ochlerotatus triseriatus'' synonym ''Aedes'' ''triseriatus''). La Crosse encephalitis virus (LACV) is one of a group of m ...
. It also occurs throughout the summer (May until September), or even throughout the year rather than mostly in August, which may be due to the diversity of mosquitoes it can infect. ;Increasing awareness and more testing In the latest US review covering 2000–2013, more than half of cases were identified in 2013 alone, the first year the CDC implemented routine JCV IgM antibody testing. ;Geography Historically, most cases of encephalitis reported to the CDC occurred in the north of the mainland United States. JCV disease most likely has a broader distribution, but is unidentified and under-reported, because testing is not considered and not straightforward. In 2013, of 10 states reporting cases, eight states reported their first JCV cases: Georgia, Idaho, Massachusetts, Minnesota, New Hampshire, Oregon, Pennsylvania, and Rhode Island. In August 2015, the Iowa Department of Public Health confirmed one case of JCV. In July 2017, the Maine Center for Disease Control announced what is believed to be Maine's first known case. ;Season Historically disease was reported to occur from late spring through early fall. However, for 2013, dates of illness onset ranged from January through November, with 14 (64%) of the 22 cases occurring during July until September.


References


Further reading

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External links


The Encephalitis Society
A comprehensive resource on Encephalitis and providing support and information to those affected and their families {{DEFAULTSORT:Jamestown Canyon Orthobunyaviruses Viral encephalitis