West Nile virus

West Nile virus
Virus classification
Group: Group IV ((+)ssRNA) Family: Flaviviridae Genus: Flavivirus Sero complex: Japanese encephalitis
Species
West Nile virus, lineage 1 West Nile virus, lineage 2

West Nile virus (WNV), may cause severe, persistent or fatal disease, although about 80% of infections are asymptomatic. It is found throughout much of Asia, Europe, Africa, Australia and North America. In 2006 in the United States, 174 deaths, 1455 cases of West Nile encephalitis/meningitis, and 2612 cases of West Nile Fever were reported to the Center for Disease Control.

Signs and symptoms

WNV is a neurotropic disease that attacks the central nervous system. The virus has an incubation time ranging from 3 to 15 days. Though the virus has shown to cause mortality among varied species of birds, it appears that it may only cause mild to moderate flu-like symptoms in humans that become infected. However, this excludes the elderly or those with weak immune systems, such as HIV or cancer, allowing the virus to more easily penetrate the blood-brain barrier and they therefore more often present with severe cases of the neurological disease. The most typical symptoms of classic WN fever include:

• fever
• headaches
• body aches

Other symptoms include:

• nausea
• vomiting
• swollen lymph glands
• rashes around the torso
• eye pain
• gastrointestinal problems

More sever neurological symptoms may also include tremor (80% or more of patients), muscle weakness, neck stiffness, stupor, coma, vision loss, numbness, febrile illness, severe muscle weakness and altered mental status. Neurological effects may be permanent. In the more serious cases, illness can advance to viral encephalitis or aseptic meningitis, as well as Guillain–Barré syndrome linked with fever or acute flaccid paralysis making it necessary to be placed on a ventilator. In two cases in the in New York City 1999 outbreak, brain scans showed swelling of the leptomeninges, and of the periventricular areas.

Transmission and Spread of West Nile virus

West Nile virus was first isolated in Uganda in 1937. Since then, there have been numerous epidemics of the virus in Israel (1950s),France (1962), South Africa (1974), and Romania (1996). Most recently, there were two epidemic outbreaks in 1999: One in Russia, and the second in the New York City area (NY99);the first time that the virus has appeared in the Western hemisphere. In NYC, 62 people were infected and six died from the disease.

It is not yet known how the virus was introduced to the US, though it has been hypothesized that the cases found in the US can be attributed to the strain of the WNV that had been spreading in the Mediterranean region since 1998. Since the initial outbreak in 1999, there have been 23,975 reported human cases by the CDC of the virus and 962 deaths around the world through 2006.

The virus is primarily transmitted to humans by the Culex pipiens and Culex. quinquefasciatus species of mosquitoes . Birds serve as a natural reservoir, with humans, horses and other mammals acting as incidental, dead-end hosts. Although primarily transmitted to humans by mosquitoes, the virus can be transmitted from human to human by blood transfusion, organ tranplantation, and by pregnant women may pass the infection to their child via intrauterine delivery. West Nile virus infects at least 300 bird species, 60 mosquito species, and 30 animal species. After research was conducted on the species of mosquitoes that carry the virus, scientists claimed that the rapid spread may be due to the hybridization of the Culex pipiens species of mosquitoes. It is believed by some researchers that the mosquitoes in Europe feast on either humans or animals, but not both, thereby limiting the spread of the virus. They hypothesis that the hybridization of US mosquitoes has led to their feasting of both humans and animals, and allows for the spread of the virus from species to species.

Clinical symptoms track closely with the particular strain of the West Nile fever infection and two major lineages have been described. Lineage II strains are found primarily in Africa and Madagascar while lineage I strains are widely distributed across North America, Europe and Africa. Virus strains found in North America are particularly neuroinvasive. At present, no vaccines for humans or antiviral agents exist for WNV and its spread can, therefore, not be stopped, but only slowed. However, there are vaccines available for horses and birds. For now, recovery from the virus is dependant on the body’s own immune response and production of IgM antibodies.

Virology and Genome of West Nile virus

West Nile virus, a flavivirus (family Flaviviridae, genus Flavivirus), is a small, enveloped, single-stranded, positive-sense RNA virus, with a genome of 11,029 neucleotide bases. West Nile virus belongs to the Japanese encephalitis serocomplex (antigenic complex) of flaviviruses and is closely related to Japanese encephatitis virus, Kunjin virus, St. Louis encephalitis virus, Murray valley encephalitis virus, Usutus virus, Cacipacore virus, Koutango virus, Yellow Fever Virus, Yaounde virus and Dengue Virus.

Within the virus genome there is a 5’ noncoding region of 96 nucleotide bases, followed by an ATG initiation codon, and then a single open reading frame of 10,302 nucleotides. Within this reading frame, the West Nile virus RNA encodes for the production of a polyprotein, which is then cleaved into ten proteins. Of these, three are structural proteins, the capsid protein, the membrane protein, and the envelope protein, which together encapsulate and protect the viral RNA by forming a viral particle about 50 nm in diameter. The other seven encoded proteins are nonstructural. The genome is then completed by a 3’ noncoding region of 631 nucleotide bases. The viral particles multiply in tissue and lymphodes near the site of infection, and travel to the blood via lymphacytes. Viremia is detected early in the infection.

It has been discovered that the West Nile strain as well as other strains of the Flavivirus have employed dual methylation of the viral RNA cap at guanine N-7 and ribose 2_-O positions with the use of methytransferase (MTase). If there is a mutation found in both of these methylation points, it is lethal to the virus. The discovery of the sites where the virus methylation occurs presents great significance in the path of creating a vaccine for the West Nile Virus because when this mutated strain is cultured in mice, it serves to protest the mice from infection of the wild-type West Nile Virus. Researchers have also identified the ENV protein as a major contributor to the immune response to the WNV and that it may therefore contribute to the existence of the many strains of the virus due to its susceptibility to mutation. “Glycosylation of ENV protein can influence virus infectivity and has been considered a potential determinant of virulence in a mouse model.” However, other cases of mutation and formation of different strains can be explained by genetic drift and native adaptation of the virus within hosts.

Prevention

As West Nile virus can be spread in blood products, screening donors may be effective. Controlling mosquito populations may be the best preventative measure for controlling the spread of West Nile virus.

Current Research

“Rapid Detection of West Nile Virus from Human Clinical Specimens”

The WNV can only be differentiated form SLE virus and JE by testing the cerebral spinal fluid, tissue or serum of those infected for the WNV-specific neutralizing antibody. However, this process can take up to a week to complete in order to properly diagnose the virus. Reverse transcriptase (RT)-PCR is another method used to identify the virus, however this method proved to be unreliable in the identifying the virus in the 1999 epidemic in New York. The reason for this is that the primers used for this method were isolated from genomic fragments of a strain of the WNV found in Uganda in 1939. The use of these primers to identify the virus in 1999 caused six misdiagnoses because the two strains only show 79% similarity. In order to better identify the strain found in New York city in 1999, researchers developed a new diagnostic assay employing fluorescent DNA probes in a 5’ exonuclease assay (TaqMan). “These TaqMan detection assays offer the advantage over traditional RT-PCR of increased sensitivity, higher throughput, increased reproducibility, and better quantitation.” They designed this new TaqMan assay to specifically identify the WNV strain found in 1999 (NY99) with 100% accuracy in humans, and proved more useful than the RT-PCR in identifying different strains of WNV and in eliminating similar viruses such as SLE Virus. It also showed to better identify the virus in avian and mosquito tissue better than the RT-PCR.

“Temperature, Viral Genetics, and the Transmission of West Nile Virus by Culex pipiens Mosquitoes”

Researchers wanted to determine if there is a significant difference between the 1999 (NY99) stain of WNV and the 2002 strain of WNV (WN02) as well as to see the relationship between temperature and transmission of the two strains. Culex pipiens mosquitoes were colonized for this purpose and were given infected to goose blood to feast on. The goose blood was either infected with NY99 or WN02 strains of the virus. They tested the mosquitoes on days 4, 7, 10, 14, 18, 21, 24, 28, 31, 34, and 40 after feasting and at 15oC, 18oC, and 22oC. Their results showed that time and temperature made little difference in the infection rate of the mosquitoes themselves. However, researchers found that the mosquitoes success at infecting humans was significantly higher for the WN02 strain than the NY99 strain at all incubation times and temperatures and in fact, the infection rate of humans rose with time and temperature. Thus, mosquitoes infected with WN02 were infected faster and transmitted the virus faster than those infected with NY99 and this speed increased even more so with rising temperatures. This may be cause for concern about the increase in WNV replication and transmission due to global warming. In addition, this study suggests the ability of a virus to evolve and adapt to new environments, rather than dying out due to of environmental changes.

External links

CDC summary==Signs and symptoms==