Powassan virus

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Powassan virus
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Flasuviricetes
Order: Amarillovirales
Family: Flaviviridae
Genus: Flavivirus
Species:
Powassan virus
Member viruses [1]

Powassan virus (POWV) is a Flavivirus transmitted by ticks, found in North America and in the Russian Far East. It is named after the town of Powassan, Ontario, where it was identified in a young boy who eventually died from it. It can cause encephalitis, inflammation of the brain. No approved vaccine or antiviral drug exists. Prevention of tick bites is the best precaution.

Contents

Classification and occurrence

Powassan virus (POWV) is a Flavivirus named after the town of Powassan, Ontario, Canada, where it was identified in a 5-year-old boy, Lincoln Byers, who died from encephalitis in 1958. [2] [3] The ICTV species name for the Powassan Virus is Orthoflavivirus powassanense. [4] The virus exists in North America and causes long-term neurological sequelae. [5] [6] [7] The first human case in the United States was found in 1970 in New Jersey and in Russia in 1978. [2] As of 2010, Powassan virus has been noted as the only tick-borne Flavivirus in North America with human pathogenicity. [8]

Powassan virus is also found in the warm climate across Eurasia, where it is part of the tick-borne encephalitis virus-complex. [9] It is found in the Russian Far East (Primorsky Krai) and appears to have been introduced there 70 years ago. [10]

Evolution

Powassan virus is an RNA virus split into two separate lineages: Lineage I, labeled as the "prototype" lineage; and Lineage II, the deer tick virus (DTV) lineage. [9] Lineage II has the most genetic variation, which indicates that it is most likely the ancestral lineage that split as a result of positive natural selection. [9] DTV is very closely related to Powassan virus and a sequence analysis showed that the two viruses diverged about 200 years ago. [11] Even though Lineage II has been predominant in POWV positive tick pools, both lineages have had confirmed cases of human disease in North America and Russia [7] [12] The lineages share 84% nucleotide sequences and 94% amino acid sequence identity. [9] Cross-neutralization occurs among flaviviruses due to the conservation of the envelope protein; this is what contributes to the fact that the two lineages are "serologically indistinguishable." [6] As a result, the lineages are part of the same viral species. [10]

According to the last data, [13] evolutionary rate of Powassan virus is 3.3 × 10−5 nucleotide substitution per site per year (95% HPD, 2.0 × 10−5–4.7 × 10−5), which is significantly lower than values reported in the previous studies. [11] [14] The values is compatible with that of tick-borne encephalitis virus (TBEV) and louping-ill virus (LIV) (1.0 × 10−5–2.2 × 10−5 for TBEV [15] [16] and 5.7 × 10−6–3.9 × 10−5 for LIV [17] ).

The most recent common ancestor of modern POWV split into two independent genetic lineages between 2600 and 6030 years ago probably as a result of the Beringia flood about 11.72 thousand years ago. [13]

Vectors

The virus can be transmitted with bites from altogether six known species of ticks; the following four species of Ixodes ticks: Ixodes cookei , Ixodes scapularis , Ixodes marxi and Ixodes spinipalpus and the ticks Dermacentor andersoni and Dermacentor variabilis . [6]

People with POWV have been mostly confirmed as having one strain of POWV, the deer tick virus. [9] I. scapularis is an important vector for the deer tick virus, which plays a vital role in maintaining the POWV. [9] I. scapularis is also a primary vector for the agent of Lyme disease, because they are generalist feeders and readily bite humans. [7]

In Canada and the Northeastern United States Ixodes cookei is the predominant species, while I. scapularis is a significant vector in Minnesota and Wisconsin. [7] POWV is transmitted when an infected tick bites a mammal; in humans the tick is typically I. scapularis. [18] In North America, the lineages of the POWV are maintained in three main enzootic cycles [9] involving three different tick species and their respective small to medium-sized woodland mammals. [9] POWV may infect I. cookei and woodchucks, or it may infect I. marxi and squirrels, and it can cycle between I. scapularis and white-footed mice. [12]

Based on the time interval for other tick-borne diseases like Lyme disease and anaplasmosis, the time interval for transmission of POWV is expected to be less than 12 hours. [19] Once the POWV reaches humans it cannot be transmitted to a feeding tick, therefore humans are considered "dead-end" hosts. [12] As of 2004, the fastest transmission time of DTV from a I. scapularis nymph to a mouse was no more than 15 minutes. [20]

Symptoms

Powassan virus infection is rarely diagnosed as a cause of encephalitis; however, when it is, Powassan encephalitis is severe, and neurologic sequelae are common. [6] Powassan encephalitis has symptoms compatible with acute disseminated encephalomyelitis, oftentimes making it difficult to diagnose. [6] Powassan virus encephalitis is a challenge to diagnose because there are only a few laboratories that offer testing, the most effective being serologic testing. [21]

There are currently no medications or approved vaccines to treat or prevent the POWV. People affected by Powassan virus generally first show symptoms 1 to 3 weeks after infection. [7] The initial symptoms include fever, headache, nausea, occasional confusion, and weakness. [12] With severe Powassan illnesses the victims should be hospitalized, because the symptoms do worsen. If not treated, symptoms could extend to meningoencephalitis, which may include: seizures, aphasia, cranial nerve palsies, paresis and altered mental status. [7] [12] Currently, the best ways to treat POWV illnesses include medications to reduce brain swelling, respiratory support and intravenous fluids. [12] About 10% of POWV encephalitis cases are fatal and half the survivors have permanent symptoms that affect their brain. [19]

Reported cases (2001–present)

There were 33 confirmed cases of Powassan virus infection in the U.S. between 2001 and 2010. [7]

A rare case of a five-month-old Connecticut infant boy contracting Powassan virus infection was published in 2017. He survived with normal motor and verbal development on follow-up at the age of 10 months, but a head MRI showed severely abnormal brain conditions, including scarring (gliosis) and softening (encephalomalacia) in the thalamus and basal ganglia on both sides, and volume loss and early mineralization in the left basal ganglia. [22]

On October 28, 2019, former U.S. Senator Kay Hagan died after contracting Powassan virus in 2016. She was 66 years old. [23]

In May 2022, the Connecticut Department of Public Health confirmed that a man aged in his 50s contracted Powassan virus in the state during March and was hospitalised with severe neurological symptoms, though he was later discharged from hospital to recover at home. [24] In May 2023, the Maine Center for Disease Control and Prevention reported that a 58-year-old adult male from Sagadahoc County died from Powassan virus. [25]

Epidemiology

Powassan Virus (POWV) is the only tick-borne flavivirus endemic in North America. [2] POWV human illnesses have been reported in the United States, Canada and Russia. [2] POWV has different genetic variations including deer tick virus (DTV) which is transmitted by the black-legged tick (aka deer tick), Ixodes scapularis . [26] It has two distinct lineages. POWV lineage I is transmitted by the Ixodes cookei which is endemic in the Great Lakes region of the United States. [3] POWV lineage II is transmitted by Ixodes scapularis which is endemic in the Northeast United States. [3] Humans can become infected in 15 to 30 minutes after tick attachment. [3] [2] [27]

Ixodes ticks have three life stages that require a host: larva, nymph and adult. [28] Each stage requires a blood meal to progress to the next life stage. The nymph stage frequently bites humans and is the stage in which I. scapularis is most likely to infect a human host with a pathogen. [29] The most common reservoir (or host) for I. scapularis are white-footed mouse and white-tail deer. [3] [30] The most common reservoirs for I.cookei are skunks, woodchucks and squirrels. [3] Humans are incidental hosts which means the ticks do not need to feed on humans to survive, humans are merely the host they find at the time for their next blood meal. [31]

In the US, the highest incidence of POWV is in Minnesota and Wisconsin, with Massachusetts and New York also having higher incidence than other states in the Great Lakes or Northeast region. [2] POWV was included in the list of nationally notifiable diseases to the U.S. Centers for Disease Control and Prevention (CDC) in 2002. [31] Between 2009 and 2018, 133 cases of neuroinvasive POWV and 12 cases of non-neuroinvasive POWV were reported to the CDC. [32] Since its discovery in 1958, there have only been 150 reported human illnesses caused by POWV. [2] The incidence rate of POWV in the United States was 1 case per year from 1958 to 2005, and has risen to an average of 10 cases per year since then. [2]

Currently, POWV is detected with IgM antibody capture ELISA of an IgM immunofluorescence antibody (IFA) assay, plaque reduction neutralization test (PRNT), detection of virus-specific nucleic acids, isolation in culture, or a >4-fold increase in antibody titers from paired acute and convalescent sera. [33] These specific tests for POWV can only be done at a state lab or the CDC. [2] Diagnostic criteria as set by the CDC are: resides in an endemic area, reported tick exposure, and presented with fever, altered mental status, seizures and focal neurological deficits and blood, tissue or cerebrospinal fluid (CSF) are positive on Powassan IgM or Powassan PRNT tests. [3] [2]

Research

Scientists at Vaccine and Immunotherapy Center at The Wistar Institute have designed and tested the first-of-its-kind synthetic DNA vaccine candidate against Powassan virus (POWV), targeting portions of the virus envelope protein. [34] [35]

Related Research Articles

<i>Flaviviridae</i> Family of viruses

Flaviviridae is a family of enveloped positive-strand RNA viruses which mainly infect mammals and birds. They are primarily spread through arthropod vectors. The family gets its name from the yellow fever virus; flavus is Latin for "yellow", and yellow fever in turn was named because of its propensity to cause jaundice in victims. There are 89 species in the family divided among four genera. Diseases associated with the group include: hepatitis (hepaciviruses), hemorrhagic syndromes, fatal mucosal disease (pestiviruses), hemorrhagic fever, encephalitis, and the birth defect microcephaly (flaviviruses).

<i>Flavivirus</i> Genus of viruses

Flavivirus, renamed Orthoflavivirus in 2023, is a genus of positive-strand RNA viruses in the family Flaviviridae. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cause encephalitis, as well as insect-specific flaviviruses (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus (PCV), and Parramatta River virus (PaRV). While dual-host flaviviruses can infect vertebrates as well as arthropods, insect-specific flaviviruses are restricted to their competent arthropods. The means by which flaviviruses establish persistent infection in their competent vectors and cause disease in humans depends upon several virus-host interactions, including the intricate interplay between flavivirus-encoded immune antagonists and the host antiviral innate immune effector molecules.

<span class="mw-page-title-main">Arbovirus</span> Class of viruses which are transmitted by arthropods

Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term arbovirus is a portmanteau word. Tibovirus is sometimes used to more specifically describe viruses transmitted by ticks, a superorder within the arthropods. Arboviruses can affect both animals and plants. In humans, symptoms of arbovirus infection generally occur 3–15 days after exposure to the virus and last three or four days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and viral hemorrhagic fever may also occur.

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. They are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. The economic impact of tick-borne diseases is considered to be substantial in humans, and tick-borne diseases are estimated to affect ~80 % of cattle worldwide. Most of these pathogens require passage through vertebrate hosts as part of their life cycle. Tick-borne infections in humans, farm animals, and companion animals are primarily associated with wildlife animal reservoirs. Many tick-borne infections in humans involve a complex cycle between wildlife animal reservoirs and tick vectors. The survival and transmission of these tick-borne viruses are closely linked to their interactions with tick vectors and host cells. These viruses are classified into different families, including Asfarviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, and Flaviviridae.

<span class="mw-page-title-main">Tick-borne encephalitis</span> Medical condition

Tick-borne encephalitis (TBE) is a viral infectious disease involving the central nervous system. The disease most often manifests as meningitis, encephalitis or meningoencephalitis. Myelitis and spinal paralysis also occurs. In about one third of cases sequelae, predominantly cognitive dysfunction, persist for a year or more.

<i>Tick-borne encephalitis virus</i> Species of virus

Tick-borne encephalitis virus (TBEV) is a positive-strand RNA virus associated with tick-borne encephalitis in the genus Flavivirus.

<span class="mw-page-title-main">Kyasanur Forest disease</span> Human disease

Kyasanur forest disease (KFD) is a tick-borne viral haemorrhagic fever endemic to South-western part of India. The disease is caused by a virus belonging to the family Flaviviridae. KFDV is transmitted to humans through the bite of infected hard ticks which act as a reservoir of KFDV.

<i>Borrelia burgdorferi</i> Species of bacteria

Borrelia burgdorferi is a bacterial species of the spirochete class in the genus Borrelia, and is one of the causative agents of Lyme disease in humans. Along with a few similar genospecies, some of which also cause Lyme disease, it makes up the species complex of Borrelia burgdorferi sensu lato. The complex currently comprises 20 accepted and 3 proposed genospecies. B. burgdorferi sensu stricto exists in North America and Eurasia and until 2016 was the only known cause of Lyme disease in North America. Borrelia species are Gram-negative.

<i>Ixodes scapularis</i> Species of tick

Ixodes scapularis is commonly known as the deer tick or black-legged tick, and in some parts of the US as the bear tick. It was also named Ixodes dammini until it was shown to be the same species in 1993. It is a hard-bodied tick found in the eastern and northern Midwest of the United States as well as in southeastern Canada. It is a vector for several diseases of animals, including humans and is known as the deer tick owing to its habit of parasitizing the white-tailed deer. It is also known to parasitize mice, lizards, migratory birds, etc. especially while the tick is in the larval or nymphal stage.

Powassan encephalitis, caused by the Powassan virus (POWV), a flavivirus also known as the deer tick virus, is a form of arbovirus infection that results from tick bites. It can occur as a co-infection with Lyme disease, as both are transmitted to humans by the same species of tick. Over the last decade, there has been a surge in the number of cases and an expansion of its geographic range. In the United States, cases have been documented primarily in the northeast. The disease was first isolated from the brain of a boy who died of encephalitis in Powassan, Ontario, in 1958. This disease is classified as a zoonosis, originating in animals, often found in rodents and ticks, with subsequent transmission to humans. The virus shares antigenic similarities with the Far Eastern tick-borne encephalitis viruses.

<span class="mw-page-title-main">Human granulocytic anaplasmosis</span> Medical condition

Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium that is typically transmitted to humans by ticks of the Ixodes ricinus species complex, including Ixodes scapularis and Ixodes pacificus in North America. These ticks also transmit Lyme disease and other tick-borne diseases.

Ticks are insects known for attaching to and sucking blood from land-dwelling animals. Ticks fall under the category of 'arthropod', and while they are often thought of in the context of disease transmission, they are also known to cause direct harm to hosts through bites, toxin release, and infestation. Infestation can cause symptoms ranging from mild to severe and may even cause death. Hosts can include any number of vertebrates, though humans and livestock are more likely to be the interest of researchers.

<span class="mw-page-title-main">Deer tick virus</span> Pathogenic member virus of Powassan virus

Deer tick virus (DTV) is a virus in the genus Flavivirus spread via ticks that causes encephalitis.

Rocio viral encephalitis is an epidemic flaviviral disease of humans first observed in São Paulo State, Brazil, in 1975. Low-level enzootic transmission is likely continuing in the epidemic zone, and with increased deforestation and population expansion, additional epidemics caused by Rocio virus are highly probable. If migratory species of birds are, or become involved in, the virus transmission cycle, the competency of a wide variety of mosquito species for transmitting Rocio virus experimentally suggest that the virus may become more widely distributed. The encephalitis outbreak in the western hemisphere caused by West Nile virus, a related flavivirus, highlights the potential for arboviruses to cause severe problems far from their source enzootic foci.

Langat virus (LGTV) is a virus of the genus Flavivirus. The virus was first isolated in Malaysia in 1956 from a hard tick of the Ixodes genus. This virus is antigenically related to Omsk hemorrhagic fever virus, Kyasanur forest disease virus, Alkhurma virus, Louping ill virus and other viruses of the tick-borne encephalitis virus (TBEV) complex. The Langat virus does not pose a significant epidemiological threat in comparison with TBEV. There are no known cases of human diseases associated with LGTV. The Malaysian strain is naturally attenuated and induces neutralizing antibodies to tick-borne encephalitis virus (TBEV) and protection against other TBEV complex viruses in animals.

Spondweni virus is an arbovirus, or arthropod-borne virus, which is a member of the family Flaviviridae and the genus Flavivirus. It is part of the Spondweni serogroup which consists of the Sponweni virus and the Zika virus (ZIKV). The Spondweni virus was first isolated in Nigeria in 1952, and ever since, SPONV transmission and activity have been reported throughout Africa. Its primary vector of transmission is the sylvatic mosquito Aedes circumluteolus, though it has been isolated from several different types of mosquito. Transmission of the virus into humans can lead to a viral infection known as Spondweni fever, with symptoms ranging from headache and nausea to myalgia and arthralgia. However, as SPONV is phylogenetically close to the ZIKV, it is commonly misdiagnosed as ZIKV along with other viral illnesses.

Royal Farm virus, previously known as Karshi virus, was not viewed as pathogenic or harmful to humans. Although infected people suffer with fever-like symptoms, some people in Uzbekistan have reported with severe disease such as encephalitis and other large outbreaks of fever illness connected infection with the virus.

<i>West Nile virus</i> Species of flavivirus causing West Nile fever

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 virus is primarily transmitted by mosquitoes, mostly species of Culex. The primary hosts of WNV are birds, so that the virus remains within a "bird–mosquito–bird" transmission cycle. The virus is genetically related to the Japanese encephalitis family of viruses. Humans and horses both exhibit disease symptoms from the virus, and symptoms rarely occur in other animals.

<span class="mw-page-title-main">NITD008</span> Chemical compound

NITD008 is an antiviral drug classified as an adenosine analog. It was developed as a potential treatment for flavivirus infections and shows broad spectrum antiviral activity against many related viruses such as dengue virus, West Nile virus, yellow fever virus, Powassan virus, hepatitis C virus, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus, and Zika virus. However, NITD008 proved too toxic in pre-clinical animal testing to be suitable for human trials, but it continues to be used in research to find improved treatments for emerging viral diseases.

<i>Modoc virus</i> Species of virus

Modoc virus (MODV) is a rodent-associated flavivirus. Small and enveloped, MODV contains positive single-stranded RNA. Taxonomically, MODV is part of the Flavivirus genus and Flaviviridae family. The Flavivirus genus includes nearly 80 viruses, both vector-borne and no known vector (NKV) species. Known flavivirus vector-borne viruses include Dengue virus, Yellow Fever virus, tick-borne encephalitis virus, and West Nile virus.

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