by Microbiology Doctor-Dr
Overview of West Nile Virus (WNV)
- The West Nile Virus (WNV) is a mosquito-borne neurotropic virus of the family Flaviviridae. It was first reported in the West Nile province of Uganda in 1937.
- The pathogen is maintained through the mosquito-bird-mosquito (enzootic) transmission cycle with Culex mosquitoes primarily acting as the vectors, birds as the natural reservoirs, and occasional spill-over from the transmission cycle affecting humans and horses.
- The infected horses as well as the humans act as “dead-end” hosts as neither of them develops sufficient viremia to transmit the virus to others.
- The virus is related to other viruses causing yellow fever and dengue fever and is more closely related to viruses causing encephalitis.
Table of Contents
Structure of West Nile Virus (WNV)
- The single-stranded, positive-sense RNA genome of the West Nile virus is joined with the capsid to create the nucleocapsid, which has an icosahedral symmetry.
- An envelope-like lipid bilayer encircles the nucleocapsid. The mature virions have a spherical form with a diameter of 40–50 nm.
- As protruding spikes, the glycoproteins on the envelope aid in the viral attachment to the host cells.
Genome structure of West Nile Virus
- Positive-stranded single-stranded RNA makes up the WNV genome.
- The RNA is made up of a single open reading frame and is around 11 kilobases in length.
- It does not have a polyadenylated tail at the 3' end, but rather has untranslated regions (UTRs), which are non-coding sections that help in replication, transcription, translation, and packaging at the 3' and 5' ends.
- The viral and host proteases convert the viral RNA into a single polyprotein.
- Three structural proteins—the capsid, envelope, and pre membrane—as well as seven nonstructural ones—NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5—are all encoded by the genome.
- The structural proteins that help in viral entry, fusion, and encapsidation are encoded at the 5' end.
- The 3' end of the genome encodes nonstructural proteins, which play a variety of roles in genome replication.
Epidemiology of West Nile Virus
- In Uganda, a feverish lady was the source of the WNV's initial isolation in 1937.
- Before the beginning of the 1990s, there were not many outbreaks of the virus in populations of humans and horses.
- Except for the outbreaks that caused encephalitis in both human and horse populations in Israel in the 1950s and France in the 1960s, symptoms in human populations were often mild with only sporadic neurologic signs.
- The 1990s saw a variety of epidemics that led to significant human illnesses, including neurological symptoms and mortality, in Algeria, Morocco, Tunisia, Italy, France, Romania, Israel, and Russia.
- The virus was originally identified in New York City before spreading over the following ten years throughout the country and into countries including Canada, Mexico, and the Caribbean.
Transmission of West Nile Virus
The enzootic cycle is where the West Nile Virus spreads.
During the process of feeding on blood, an infected mosquito vector transmits the virus to its vertebrate victims.
While other Aedes species that resemble mosquitoes can also act as bridge vectors, Culex mosquitoes are the main carriers of viral transmission.
A few other ways for the transmission to happen are as follows:
- Organ transplants and blood transfusions
- infection with the virus in labs
- pregnant woman to child during birth or nursing
The WNV does not, however, spread through:
- sneezing, sniffling, or touching contaminated individuals
- contact with living animals
- handling sick birds that are alive or dead (However, the use of gloves and plastic bags for disposing of the dead birds are recommended, and touching the dead animals with bare hands must be avoided as far as possible)
- eating animals with disease (Proper instructions must be followed while cooking the meat)
Replication of West Nile Virus
- Attachment/Adsorption
It is still unclear exactly what the WNV receptor is. However, many glycosaminoglycans, the mannose receptor, DC-SIGN, and other molecules may act as the virus's receptors.
- Penetration
- Uncoating
The E protein undergoes conformational changes as a result of the acidification of the endosomal compartment, which leads to the fusing of the viral membrane with the membrane of the endosomal compartment. The viral nucleocapsid is then released into the cytoplasm as a result.
- Biosynthesis
A single polyprotein made from the viral RNA is processed. Genome replication occurs in certain viral protein domains. The Endoplasmic reticulum undergoes significant growth and alteration as a result of the viral proteins. Vesicle packets (VP) and convoluted membranes (CM) are the two crucial domains for viral replication and protein processing, respectively.
- Assembly
The Golgi apparatus is where the viral assembly takes place once the virus buds off at the endoplasmic reticulum.- Maturation
The immature virion's prM protein is broken down in the Golgi apparatus during viral maturation, releasing the mature viral particle into the cytoplasm.
- Release
Exocytosis is the process by which the virus particle leaves the cell after travelling to the cell surface in an exocytic vesicle.
Pathogenesis of West Nile Virus
- Due to the variations in viral strains and the rarity of laboratory-confirmed human infections, it has been challenging to pinpoint the specific pathophysiology of the virus in people.
- The research of animal models infected under carefully monitored laboratory circumstances has provided the majority of our information about WNV pathogenesis.
- During a blood meal, an infected mosquito injects its saliva into the human host, where it is then deposited in the blood and skin tissue.
- The virus subsequently spreads to the lymph nodes by infecting nearby dendritic cells similar to Langerhans cells.
- It multiplies in the tissues and results in a brief case of viremia, which usually lasts a couple of days.
- The virus that lowers the viral load during viremia is targeted by anti-WNV IgM antibodies.
- The virus then spreads to several bodily organs including the spleen, liver, and kidneys.
- Eight days after the beginning of symptoms, the virus can be found in the urine of a patient with encephalitis and the viral infection of the kidneys.
- Because the virus may pass across the blood-brain barrier (BBB), it might cause neurological problems.
- However, it could enter the CNS without affecting the BBB.
- The immunological reaction of the host is connected to the WNV pathogenesis as well.
Clinical Manifestations of West Nile Virus
20 percent of those infected can develop West Nile fever or severe West Nile illness, while around 80 percent of those infected remain asymptomatic.
Typically, the incubation phase lasts 3 to 14 days.
However, immunocompromised people have been shown to have a longer incubation time of roughly 21 days.
The following are typical signs of the febrile illness:
- Headache
- Body aches
- Fever
- Joint pain
- Vomiting
- Diarrhea
- Occasional skin rash (on the trunk of the body)
- Swollen lymph glands
Along with other names including West Nile encephalitis, meningitis, or West Nile poliomyelitis, the severe WNV sickness is also known as the neuroinvasive disease.
According to estimates, a severe variant of the WNV infection develops in around 1 in 150 afflicted individuals.
The following are some signs of the severe illness:
- Headache
- High fever
- Neck stiffness
- Stupor
- Disorientation
- Coma
- Tremors
- Convulsions
- Muscle weakness
- Paralysis
- Myelitis
- Optic neuritis
- Rhombencephalitis
- Polyradiculitis
Rare additional neurological symptoms such myocarditis, pancreatitis, and fulminant hepatitis have also been documented.
Patients of any age might develop the serious sickness. However, those over the age of 60, those who are immunocompromised, and those who have specific diseases—such as cancer, diabetes, hypertension, renal disease, etc.—are more likely to have severe sickness as a result of an infection.
Diagnosis of West Nile Virus
Antibody Detection
The identification of anti-WNV IgM antibodies in the serum and cerebrospinal fluid is a key component in the diagnosis of WVV infection (CSF). Through the use of the IgM-capture enzyme-linked immunosorbent assay, a serological test is conducted (ELISA). A previous infection may also be indicated by the presence of WNV-specific IgM antibodies, which are typically detectable 3 to 8 days after infection and may persist for 30 to 90 days. Because IgM antibodies cannot pass the blood-brain barrier, intrathecal IgM can be a sign of WNV infection in the central nervous system.
Plaque-reduction neutralization tests (PRNTs)
The reference laboratories, which include the CDC and a few state public health laboratories, carry out PRNTs. The test aids in identifying the particular flavivirus that is causing illness. By showing a fourfold or more difference in the titer of WNV-specific neutralising antibodies between serum samples taken during the acute and convalescent phases, which were obtained two to three weeks apart, PRNTs can also confirm acute infections.
Other tests
- For blood, CSF, and tissue samples taken in the early stages of infection, virus culture and viral RNA detection (using the reverse transcriptase-polymerase chain reaction) can be performed, and if positive, can confirm an infection.
- In formalin-fixed tissue, WNV antigens may also be found using immunohistochemistry (IHC).
- State public health laboratories or the CDC are both capable of doing viral culture, RT-PCR, and IHC. The absence of WNV infection is not completely ruled out by the negative test findings, though.
- In fatal cases, pathological signs such as inflammation of the brain and spinal cord with minor haemorrhages, perivascular cuffing, and severe neuronal degeneration can be seen by brain biopsy from surgery and autopsy.
- These are the effects of WNV replication that lead to inflammation, cytotoxic reaction, and damage.
Treatment of West Nile Virus
- Although there is no particular therapy for the WNV infection, the patient may get supportive care.
- In vitro tests have revealed that high dosages of ribavirin and interferon-b are effective against the WNV.
- However, adequate in vivo clinical testing is still needed to confirm its efficacies.
- Meningeal symptoms call for pain management, whereas nausea and vomiting symptoms call for antiemetic medication and rehydration.
- Patients with encephalitis need to be closely watched for the emergence of high intracranial pressure and seizures.
- In the event of acute neuromuscular respiratory failure, patients should be provided with ventilation assistance.
Prevention and Control of West Nile Virus
- To far, no vaccines have been approved for use in humans to protect against the WNV infection.
- Although there are legal and effective vaccinations for the treatment of horses against WNV infection, there are no FDA-approved vaccines for use in humans.
- Clinical trials are being conducted on many vaccinations to evaluate their effectiveness.
- In locations where the illness is prevalent, wearing long sleeves, long trousers, and window screens are the main ways to avoid contracting the virus in people.
- Controlling mosquito breeding grounds will help reduce the vector population, which in turn will lower transmission.
- To limit transmission during organ transplants and blood transfusions, proper screening must be conducted.
- Patients with WNV infections should wait at least 4 months after becoming unwell before giving blood.
