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Coltivirus – Structure, Genome, Replication, Pathogenesis

Coltivirus is a virus genus (of the family Reoviridae) that infects both vertebrates and invertebrates. It contains the agent that causes Colorado Lyme fever. The Colorado tick fever virus can lead to fever, shivers, headache, photophobia, myalgia, arthralgia, and fatigue. Children are especially susceptible to developing a hemorrhagic disease. Leukopenia containing both lymphocytes and neutrophils is a prevalent symptom of Colorado tick fever virus infection. In either situation, the infection may result in encephalitis or meningitis.

Coltivirus is the name of a virus genus. Viruses are intracellular parasites that lack the means to reproduce on their own, so they commandeer the machinery of a host cell in order to proliferate. Only then are they able to synthesize their viral proteins and produce their offspring. Viruses are divided into two categories based on their genetic material.

DNA viruses have genomes composed of deoxyribonucleic acid (or DNA), whereas RNA viruses, such as Coltivirus, have segmented (multipartite) RNA (ribonucleic acid) genomes.

The name “Coltivirus” derives from the type species of the genus, the Colorado tick fever virus (also known as the “Colorado tick”). Coltivirus is a member of the Reoviridae family, which consists of eight taxa. Orthoreovirus, Orbivirus, Coltivirus, Rotavirus, Aquareovirus, Cypovirus, Phytoreovirus, and Fijivirus. Coltivirus and Orbivirus comprise approximately 109 serotypes, of which only four cause human disease. The primary vectors of coltiviruses are ticks. Colorado tick fever was first documented in the nineteenth century and is now one of the most prevalent vector-borne diseases in the United States.

The European Eyach virus and the Colorado Lyme fever virus are related due to cognate genes, 55 to 88% amino acid similarity, and indistinguishable similarities at the microscopic level.[6] A genome sequence analysis was conducted to identify these similarities. The migration of lagomorphs from North America to Europe more than fifty million years ago is one of the hypotheses regarding the origin of the European Eyach virus.[6] Since then, the virus has acquired some distinctions and is now considered its own virus species. European Eyach virus was first isolated in 1976 from Ixodes ricinus ticks in Europe and again in 1981 from the same species as well as Ixodes ventallai ticks.

Coltivirus

  • Coltivirus is a genus of viruses belonging to the Reoviridae family. Coltiviruses are envelopeless arboviruses with a double-stranded RNA genome, transmitted by ticks or mosquitoes. They infect rodents and infect humans with Colorado tick fever.
  • 60-80 nm in diameter, non-enveloped, icosahedral virion with a triple capsid structure. Pentameric turrets are external to the innermost capsid. The intermediate capsid has T=13 icosahedral symmetry, whereas the inner capsid has T=2* symmetry.
  • Linear segmented dsRNA genome. Twelve segments code for thirteen proteins. The sizes of segments range from 675 to 4,350 bp, and the total genome size is approximately 29,000 bp (CTFV).
  • To prevent activation of antiviral state in response to dsRNA by the cell, the dsRNA genome is never wholly uncoated. From each segment of dsRNA, the viral polymerase VP1 generates capped mRNA. This encapsulated mRNA is transported into the cytoplasm of the cell, where it is translated. VP9 protein is expressed through RNA termination suppression.

Structure of Coltivirus

Coltivirus - Structure, Genome, Replication, Pathogenesis
Structure of Coltivirus | Image Source: https://viralzone.expasy.org/598
  • Coltivirus virions have a diameter between 60 and 80 nanometers, lack an envelope, and are typically spherical with icosahedral symmetry.
  • Each virion has two concentric capsid shells encircling a 50-nanometer-diameter nucleus.
  • The particle’s surface is relatively flat.
  • The virus loses its infectiousness when the ambient fluid becomes acidic, around a pH of 3, but is stable between pH 7 and 8.
  • Also, it ceases to be a hazard when the temperature reaches approximately 55 degrees Celsius.
GenusStructureSymmetryCapsidGenomic arrangementGenomic segmentation
ColtivirusIcosahedralT=13, T=2Non-envelopedLinearSegmented

Genome of Coltivirus

  • Coltiviruses contain twelve linear, double-stranded RNA segments.
  • When the genome is analyzed using gel electrophoresis, the segments migrate in three distinct size classes (bands).
  • Each segment is replicated, and the segment encoding RNA polymerase is the largest. Other protein locations along the genome have yet to be determined.
  • Linear segmented dsRNA genome.
  • Twelve segments code for thirteen proteins.
  • The sizes of segments range from 675 to 4,350 bp, and the total genome size is approximately 29,000 bp (CTFV).

To prevent activation of antiviral state in response to dsRNA by the cell, the dsRNA genome is never wholly uncoated. From each segment of dsRNA, the viral polymerase VP1 generates capped mRNA. This encapsulated mRNA is transported into the cytoplasm of the cell, where it is translated. VP9 protein is expressed through RNA termination suppression.

Genome map of species Colorado tick fever virus (CTFV) showing several segments.
Genome map of species Colorado tick fever virus (CTFV) showing several segments.

Replication of Coltivirus

  1. Virus endocytosis into host cells is presumably mediated by attachment to host receptors.
  2. Endolysosomes decoat particles partially, but not entirely, and allow them to enter the cytoplasm.
  3. Early transcription of the dsRNA genome by viral polymerase takes place within this subviral particle (naked core), so that dsRNA is never exposed to the cytoplasm.
  4. Synthesis of full-length plus-strand transcripts from each dsRNA segment. These plus-strand transcripts serve as translation templates.
  5. In cytoplasmic viral factories, viral proteins and genomic RNA congregate.
  6. (+)RNAs are encapsulated within a sub-viral particle, where they are transcribed to produce RNA (-) molecules with which they base-pair to generate dsRNA genomes.
  7. Capsid assembly occurs on the subviral particle.
  8. Presumably, mature virions are released following cell death and the concomitant breakdown of the plasma membrane of the host.

Pathogenesis of Coltivirus

  • The Colorado tick fever virus is spread via the bite of the Dermacentor andersoni wood tick.
  • Humans serve as secondary hosts for the virus after ticks and rodents.
  • The tick’s saliva then permanently harbors the virus, making the tick an eternal vector.
  • Following transmission from the adult tick, the virus infects human bone marrow cells.
  • Replication of the virus in bone marrow cells interferes with normal leukocyte (white blood cell), eosinophil, and basophil development and reproduction.
  • As a consequence, thrombocytopenia may occur.
  • Red blood cells, or erythrocytes, are infected when still in the nucleated erythroblast stage.
  • The virus can remain dormant in RBCs for up to four months.
  • In this environment, it is safe from the assaults of the immune system.
  • While the virus remains dormant in blood cells for up to six weeks after symptoms first appear, antibodies to the virus are not detected until around two weeks after symptoms first appear.

How does Coltiviruses Causes Infection?

Coltiviruses can infect and multiply in the cytoplasm of cells from both arthropods and vertebrates, but can only be spread by the former. Replication of the virus’s RNA requires the removal of the virion’s outer shell so that RNA polymerase can begin its work. Some of the variation in genetic makeup between serotypes can be attributed to the frequent reassortment of RNA segments in offspring. This can sometimes cause sudden shifts in the viruses’ characteristics.

The Rocky Mountain wood tick (Dermacentor andersoni) is infected with Colorado tick fever virus (CTF), the most common species of Coltivirus. This tick species thrives in areas with bushes, light woods, meadows, and pathways where people walk or ride bikes. Colorado tick fever virus can be transmitted to vertebrates via the larval, nymphal, and adult stages of this tick. As unfortunate as it may sound, mature D. andersoni prefer to prey on medium or large creatures that are wandering among the knee-high vegetation. Tick larvae commonly contract the virus through feeding on rodents (such as squirrels) who are already sick with the illness. Once the virus is in the tick’s saliva, the tick is forever infected. Following transmission from the adult tick, the virus infects human bone marrow cells.

Replication of the virus in bone marrow cells interferes with normal leukocyte (white blood cell), eosinophil, and basophil growth and replication. This may also contribute to the development of thrombocytopenia. Red blood cells, or erythrocytes, are infected when still in the nucleated erythroblast stage.Red blood cells can harbor the virus for up to four months without being damaged.It is safe from the assaults of the immune system here. While the virus remains dormant in blood cells for up to six weeks after symptoms first appear, antibodies to the virus are not detected until around two weeks after symptoms first appear.

GenusHost detailsTissue tropismEntry detailsRelease detailsReplication siteAssembly siteTransmission
ColtivirusHumans; rodents; ticks; mosquitoeErythrocytesCell receptor endocytosisCell deathCytoplasmCytoplasmArthropod bite

Epidemiology of Coltivirus

  • In the United States, the Colorado tick fever virus is found primarily between 4,000 and 10,000 feet in the Rocky Mountains. The states and provinces of California, Colorado, Idaho, Montana, Nevada, Oregon, Utah, Washington, Wyoming, British Columbia, and Alberta are among those where the Colorado tick fever virus has been documented. The accompanying image depicts the tick that transmits the virus, and its dispersion is similar to this.
  • Humans serve as secondary hosts for the virus after ticks and rodents. Hikers and campers in high-risk areas are the most likely to contract the disease.
  • Since adult ticks are most abundant in the environment during the months of April, May, and June, this is also when the illnesses typically occur.
  • Unfortunately, this is also the time of year when camping and trekking are most enjoyable. Wearing long sleeves or pants, avoiding highly infected regions, and using tick repellent are all good ways to reduce your risk of being bitten and contracting this disease.

Clinical manifestations of Coltivirus

Coltivirus infections can cause a range of clinical manifestations, although many people who become infected may not experience any symptoms at all. When symptoms do occur, they can range from mild to severe and may include:

  1. Fever: A high fever is one of the most common symptoms of coltivirus infection, and it can last for several days.
  2. Headache: Many people with coltivirus infections also experience severe headaches, which may be accompanied by sensitivity to light or sound.
  3. Muscle aches: Muscle aches and joint pain are also common symptoms of coltivirus infections.
  4. Rash: Some people with coltivirus infections may develop a rash, which can be itchy and may appear on the trunk, arms, and legs.
  5. Nausea and vomiting: Some people with coltivirus infections may experience nausea and vomiting, although these symptoms are less common.

In rare cases, coltivirus infections can lead to more severe symptoms, such as meningitis or encephalitis. These conditions can cause inflammation of the brain and can lead to neurological symptoms such as seizures, confusion, and difficulty speaking.

Vectors & Host Range

  • Coltivirus is primarily transmitted by ticks, which serve as the primary vector for the virus. The most common tick species associated with coltivirus transmission are Ixodes ricinus, Ixodes persulcatus, and Haemaphysalis concinna.
  • Coltivirus has been detected in a range of mammalian hosts, including rodents, deer, and cattle. In Europe, coltivirus infections have been reported in rodents such as bank voles, wood mice, and yellow-necked mice. In Asia, coltivirus infections have been reported in a variety of hosts, including deer, cattle, and small mammals such as shrews and hedgehogs.
  • It is important to note that although coltivirus infections have been detected in a variety of animal hosts, not all infected animals may develop symptoms or become sick. In addition, the ability of the virus to infect and transmit between different animal hosts may vary depending on the specific host and geographic region.
  • Humans can also become infected with coltivirus through tick bites or by handling infected animal tissues or fluids. While human infections with coltivirus are rare, they have been reported in Europe and Asia. The severity of human infections can vary, ranging from mild flu-like symptoms to more severe complications such as meningitis or encephalitis.

Lab Diagnosis of Coltivirus

The laboratory diagnosis of coltivirus infections typically involves detecting the presence of the virus or antibodies to the virus in a patient’s blood, cerebrospinal fluid (CSF), or other body fluids or tissues.

  • Virus isolation: The virus can be isolated from patient samples, such as blood or CSF, and grown in cell cultures. This method is time-consuming and may take several days to weeks to yield results.
  • Polymerase chain reaction (PCR): PCR can detect the genetic material of the virus in patient samples, such as blood, CSF, or tissue. This method is fast and sensitive, and can yield results in a few hours.
  • Serology: Serology involves testing for the presence of antibodies to the virus in a patient’s blood. This method is useful for detecting past infections or for confirming an acute infection when virus isolation or PCR is not available.
  • Electron microscopy: Electron microscopy can be used to directly visualize the virus in patient samples, such as blood or tissue. This method is less commonly used due to its lower sensitivity compared to PCR.

It is important to note that laboratory tests for coltivirus infections may not be widely available in all regions, and not all medical laboratories may have the capacity to perform these tests. Therefore, it is important to consult with a healthcare provider if you suspect you may have a coltivirus infection, as they can help determine the most appropriate course of diagnosis and treatment.

Treatment of Coltivirus

There is no specific treatment for coltivirus infections, and management typically involves treating the symptoms and complications of the infection.

  • Symptomatic treatment: The symptoms of coltivirus infections, such as fever and headache, can be managed with over-the-counter pain relievers, such as acetaminophen or ibuprofen. In severe cases, hospitalization may be necessary to manage symptoms and provide supportive care.
  • Antibiotics: Antibiotics are not effective against viruses, but they may be used to treat secondary bacterial infections that can occur as a result of a weakened immune system or damaged tissue.
  • Antiviral medication: There is no specific antiviral medication for coltivirus infections, although some antiviral drugs have been shown to be effective against related viruses in laboratory studies.
  • Prevention: The best way to prevent coltivirus infections is to avoid tick bites and to take appropriate precautions when handling animal tissues or fluids. If you suspect that you may have been exposed to coltivirus, it is important to seek medical attention right away.

It is important to note that coltivirus infections can sometimes lead to severe complications, such as meningitis or encephalitis. These conditions require prompt medical attention and may require hospitalization and intensive care. If you develop symptoms of coltivirus infection, it is important to seek medical attention right away to prevent serious complications from developing.

Prevention and control of Coltivirus

Prevention and control of coltivirus infections primarily involve measures to reduce exposure to ticks, which are the primary vectors of the virus. Here are some measures that can help prevent and control coltivirus infections:

  • Avoid tick-infested areas: When possible, avoid walking or hiking in areas known to be infested with ticks, particularly during the warmer months.
  • Wear protective clothing: Wear long-sleeved shirts, long pants, and closed-toe shoes when in tick-infested areas. Tucking pants into socks or boots can also help prevent ticks from crawling up your legs.
  • Use tick repellents: Use insect repellents that contain DEET or picaridin on exposed skin and clothing. Follow the manufacturer’s instructions for use.
  • Check for ticks: After spending time outdoors in a tick-infested area, thoroughly check your body for ticks. Use a mirror to check hard-to-see areas such as the back of the neck and behind the ears.
  • Remove ticks promptly: If you find a tick attached to your skin, remove it promptly using tweezers. Grasp the tick close to the skin and pull it straight out with steady, even pressure. Do not twist or jerk the tick, as this can cause the mouthparts to break off and remain in the skin.
  • Keep your yard tick-free: Keep your yard clean and free of debris, and remove leaf litter and tall grasses, which can provide habitat for ticks. You can also use tick control products in your yard, such as acaricides, to help reduce tick populations.
  • Be cautious when handling animal tissues or fluids: Wear gloves and other protective clothing when handling animal tissues or fluids, particularly those from infected animals.

It is important to note that there is currently no vaccine for coltivirus infections, so prevention and control measures primarily focus on reducing exposure to ticks. If you suspect that you may have been exposed to coltivirus, it is important to seek medical attention right away to prevent serious complications from developing.

FAQ

What is Coltivirus?

Coltivirus is a type of virus that belongs to the Reoviridae family. It is a single-stranded RNA virus that can cause infections in both humans and animals.

How is Coltivirus transmitted?

Coltivirus is transmitted through the bite of infected ticks. The primary vector of the virus is the Hyalomma tick, which is found in Africa, Europe, and Asia.

What are the symptoms of Coltivirus infection in humans?

The symptoms of Coltivirus infection in humans include fever, headache, muscle aches, joint pain, and fatigue. In severe cases, it can also lead to hemorrhagic fever and encephalitis.

How is Coltivirus diagnosed?

Coltivirus infection can be diagnosed through laboratory tests that detect the virus in blood or other bodily fluids. These tests include enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and viral isolation.

Is there a vaccine for Coltivirus?

Currently, there is no vaccine available for Coltivirus. Treatment for the infection is mainly supportive, and patients are typically given fluids, pain relief medication, and rest.

Can Coltivirus be prevented?

The best way to prevent Coltivirus infection is to avoid tick bites. This can be done by wearing protective clothing, using insect repellent, and avoiding tick-infested areas.

How common is Coltivirus infection?

Coltivirus infection is relatively rare in humans. The virus is primarily found in animals, including cattle, sheep, and goats.

Can Coltivirus be transmitted from person to person?

Coltivirus cannot be transmitted from person to person. It is only transmitted through the bite of infected ticks.

What is the prognosis for Coltivirus infection?

The prognosis for Coltivirus infection varies depending on the severity of the illness. Mild cases usually resolve on their own within a few days, while severe cases may require hospitalization and can be fatal.

Where is Coltivirus found?

Coltivirus is found in various regions around the world, including Africa, Europe, and Asia. It is primarily found in animals, including livestock, but can also infect humans who come into contact with infected ticks.

References

  • Attoui H, Mohd Jaafar F, de Micco P, de Lamballerie X. Coltiviruses and seadornaviruses in North America, Europe, and Asia. Emerg Infect Dis. 2005 Nov;11(11):1673-9. doi: 10.3201/eid1111.050868. PMID: 16318717; PMCID: PMC3367365.
  • https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=10911
  • https://viralzone.expasy.org/598
  • https://ictv.global/report/chapter/spinareoviridae/spinareoviridae/coltivirus

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