Bibliography

1. The Molecular Anatomy Project: http://maptest.rutgers.edu/drupal/?q=node/451

2. Viral Zone - Flavivirus: http://viralzone.expasy.org/all_by_species/24.html

3. http://prezi.com/fknljqlfsjma/sbi3u-module-11-west-nile-virus/

4. Induced Species Summary Project: http://www.columbia.edu/itc/cerc/danoff-burg/invasion_bio/inv_spp_summ/WestNile.html

5. Campbell Biology text book

6. Center for Disease Control and Prevention: http://www.cdc.gov/westnile/symptoms/

7. The Microbial World: http://www.microbiologytext.com/index.php?module=Book&func=displayarticle&art_id=492

8. Image source: http://www.mcb.uct.ac.za/tutorial/basic_virion_constituents.htm
9. Global Epedemic: http://www.gideononline.com/wp/wp-content/uploads/West-Nile-Fever-Map.png

Epidemiology and Public Health

The West Nile Virus was first discovered in the West Nile province of Uganda in 1937. Throughout the 20th century, it emerged as a serious cause of disease as a result of widespread epidemics in Europe and the Middle East. It did not reach the level of pandemic threat, however, until 1999, when the first case of West Nile encephalitis was confirmed in New York City. Within a year, it spread to New Jersey, Connecticut, and other areas of New York, and is now present in almost every state (1).

Figure 4.1: The spread of West Nile Virus infection across the United States from 1999 to 2004 (1). 

Figure 4.2: Disease is endemic or potentially endemic in 83 countries. As shown here, it is most common in the United States (9).

The numbers of people infected continue to rise faster than predicted. This video, aired on CNN in 2012, discusses the dramatic rise in cases in the United States: http://www.cnn.com/2012/08/22/health/west-nile-virus/

Symptoms, Treatment, and Prevention

Symptoms of infection:

• 80% of people infected with the West Nile Virus are asymptomatic (present no symptoms) (6).
• 20% develop flu-like symptoms including fever, body aches, joint pains, vomiting, diarrhea, or rash. Such febrile illness usually lasts several weeks, but results in a full recovery (6).
• Less than 1% of people infected develop a serious neurological illness, such as encephalitis or meningitis (inflammation of the brain or surrounding tissue. Symptoms include headache, high fever, neck stiffness, disorientation, coma, tremors, seizures, or paralysis. Recovery may take months, and some neurological effects are permanent. Of this category, 10% of people will die (6).

Figure 3.1: A table of cases reported to the CDC from 1999 to 2004 (1).

Treatment:
No vaccines or specific antiviral treatments have been developed for humans, though there are vaccines available for equine animals, such as horses. Intravenous fluids, pain medication, and nursing care is used to treat the symptoms of infection in severe cases (6).

Prevention:
The following are lifestyle habits that decrease the likelihood of contracting the disease (3):

• Changing bird bath water every 48 hours (prevents spread of mosquito eggs)
• Wearing light colored long sleeved clothes
• Minimizing amount of deodorant worn
• Bathing regularly
• Installing bug screens
• Using mosquito repellant
• Minimize time outdoors at dawn and dusk (mosquito’s most prevalent time of day)

Transmission and Life Cycle

The West Nile Virus is most commonly carried through mosquitos. It is transmitted when a mosquitto bites an infected bird. The virus travels through the mosquito's salivary glands into the circulatory system where it remains for a few days. It can then be released when the mosquito bites another organism. The organism which the virus is passed onto is only contagious if they are able to develop a high enough concentration of the virus in their blood (3). Its host range consists of mosquitos, birds, horses, humans, and other species (5). Birds and mosquitos are contagious, while other organisms which cannot spread the virus to other living things, such as humans and horses, are known as "dead end organisms" (3). Humans typically contract the virus from mosquitos, though 43 other species, including ticks, have been reported to serve as vectors (1).

Figure 2.1: Transmission Cycle of West Nile Virus (3).

Figure 2.2: The Culex genus of mosquitos, which serves as a primary vector in the United States (1).

Like all viruses, the West Nile Virus can only replicate in host cells because it lacks metabolic enzymes and equipment for making proteins. The virus infects a host cell by fusing to its plasma membrane, inserting its viral genome. Once inside, the protein the virus encodes can reprogram the cell to copy the viral nucleic acid and manufacture viral proteins (5). 

Viral Structure

The West Nile Virus is a member of the Flavivirus genus. Like all flaviviruses, it has a spherical envelope, and has an icosahedral nucleocapsid which contains a single-stranded RNA genome (2).

The West Nile Virus genome is about 10,000 bases long. The genome 3’ terminus end forms a loop structure, and the 5’ end has a methylated nucleotide cap which allows for translation, or a genome-linked protein (VPg) (7).

Figure 1.1: Map of a flavivifus genome (2).

The capsid has an icosahedral shape, and is about 25 nm in diameter (4).

Figure 1.2: The red depicts the envelope, cut away to show the capsid structure (8).

Viral envelopes typically help the virus infect the host and are composed of phospholipids and membrane proteins derived from host cell, and proteins and glycoproteins of viral origin. The West Nile Virus envelope is composed of proteins, lipids, trace metals, and carbohydrates, and is about 50 nm in diameter (4). The surface structure varies between immature and mature viruses (1). The immature viral envelope consists of 60 trimetric glycoprotein spikes in an icosahedral symmetric pattern. The fusion loops of each glycoprotein are pointed inward, and pre-membrane proteins (prM) are attached to the spikes, preventing the virus membrane from fusing with the cell membrane. When the virus encounters an environment of low pH, the prMs are released, allowing maturation to begin. During maturation, a conformational change occurs, rearranging the trimetric spikes to produce a smooth surface. (1)

Figure 1.3: The envelope structure of the immature virus (left) in contrast to the mature virus (right) (1).

The mature viral envelope also has an icosahedral shape, but its sets of three glycoproteins are arranged in a herringbone pattern. It contains two virus-encoded membrane proteins, the M protein and the E dimer, and180 copies of its envelope glycoprotein. The glycoproteins contain three domains (DI, DII, DIII), each having a specific role during cell entry. DII contains the fusion loop, which is responsible for the fusion of the viral envelope to the cell membrane (1).

Figure 1.4: The divisions of a single glycoprotein (1).