The Emergence of West Nile Virus

THE EMERGENCE OF WEST NILE VIRUS:

A LITERATURE REVIEW

Christopher Allan F. Reballos

INTRODUCTION

The year 1999 was an alarming year when an outbreak of arboviral encephalitis arrived in North America (Nosal and Pellizzari, 2003; Petersen et al, 2002; Scaramozzino et al, 2001). This epidemic spread rapidly across North America, namely United States and into Canada. The detection was first identified among birds and mosquitoes in the year 2001 and by the end of 2002, human infection cases were noted from nearby cities of Canada. It was identified that the human infection is caused by mosquito transmission. Migrating birds are presumed to play a significant role in facilitation of the dispersal of the virus to the mosquito population over distant locations. Though this remains the most significant vehicle for human disease, other possible means are through the blood or organ donation, pregnancy, lactation, needle-stick injury and exposure to infected laboratory specimens. The outbreak is responsible for considerable morbidity and mortality and may cause severe encephalitic, hemorrhagic, hepatic and febrile illness in vertebrates, including humans. Information was gathered from medical literature and the medical surveillance data. Petersen et al (2002) and Jupp (2001) have well documented enzootic activity of the outbreak and in New York City, it was identified to be the West Nile Virus

Genetics of West Nile Virus

West Nile Virus (WNV) is a single-stranded positive polarity RNA virus (Diamond et al, 2003). This etiologic agent of the West Nile encephalitis is a member of the family Flaviviridae (W. Li et al, 2002; Pei-Yong Shi et al, 2001 and 2002; Andersen et al, 1999;Enserinck, 1999), which comprises over 70 viruses sharing common antigenic determinants (Scaramozzino et al, 2001). The family contains eight serosubgroups and nine individual serotypes. This arthropod borne flaviruses are transmitted to vertebrates by mosquito infection or tick vectors. Many viruses that belongs to the family are significant human pathogens, which include the pathogenic viruses Yellow fever virus (YF), Dengue viruses, Tick-borne encephalitis virus (TBE), Japanese encephalitis virus (JE), St. Louis encephalitis virus (SLE).

This single-stranded plus sense non segmented RNA virus has a positive polarity genome of approximately 11,000 nucleotides or 11 Kb (Lanciotti and Kerst, 2001; Lanciotti et al 2000; Pei-Yong et al, 2002). A single, long open reading frame is contained in the genomic RNA of the flavivirus. Both termini of the genomic RNA contain 5' untranslated region (UTR) and 3'UTR sequences that do not encode viral proteins (Pei-Yong et al, 2001). Viral and cellular proteases translated and co- and posttranslationally processed that encode a single long polyprotein into three structural proteins, namely the capsid (C), premembrane (prM) or membrane (M), and envelope glycoprotein (E) and followed by seven nonstructural proteins NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5 in that order. These findings suggest that replacing the genes for the viral structural proteins in a full-length infectious cDNA clone of a flavivirus with the corresponding viral genes of another flavivirus could produce the viable virus. Test had been successfully conducted with chimeras that contained the sequence for viral structural proteins preM and E of tick-borned encephalitis virus (TBEV) or tick-borned Langat virus (LGT). Though all other sequences were derived from the full-length infectious cDNA of mosquito-borne dengue type 4 virus (DEN4). This provides information that viral structural proteins of the flavivirus could function in the context of cis-acting 5' and 3' sequences and nonstructural proteins of DEN4. This proves that the chimeras, observed among mice with respect to virulence, has the ability to spread to the central nervous system (CNS) from a peripheral site of inoculation and cause encephalitis. Nevertheless, the chimeras are said to be immunogenic. It is able to induce resistance in mice against challenge with TBEV and LGT.

West Nile cDNA contains structural preM and E proteins genes (Pletnev, 2002). When full length RNA generated by SP6 RNA polymerase was transfected into mosquito C6/36 or Vero cells, it became infectious. Analysis of plasmids DNA revealed 4 difference in nucleotide sequence from WN sequence determined by reverse transcription-PCR of WN strain obtained from New York 1999 outbreak. Three of these differences produced amino acid substitutions in preM (Ile6 Thr and Ile146 Val) and E (Thr282Ala). Also, variability between (i) Glu92 and Asp and (ii) Leu112 and Ser is identified in the DEN4 NS3 and NS4B nonstructural proteins of the WN/DEN4 clone 55. Also, sequence of the Vero cell-grown WN clone 18 differed from its progenitor plasmid cDNA sequence gene. A change U7162→ C that caused the substitution Leu112→ Ser was identified. Interestingly, a different substitution at this locus, Leu112→ Phe, was previously observed by Berthet et al.

The virions of Flavivirus (Lanciotti et al, 2000) are spherical in shape with a diameter of 40 to 60 nm. The 30 nm in diamter nucleocapsid is surrounded by a lipid bilayer with embedded viral envelope and membrane proteins and are consists of capsid and genomic RNA.

The principal features of the flavivirus multiplication cycle is the role of OAS in affecting the WN virus-host interaction. WN virions are enveloped, possess a positive-strand ssRNA genome, and multiply in the cytoplasm of infected cells (Samuel, 2002). Lanciotti et al (2000) describe the spherical enveloped with a diameter of 40 to 60 nm virion which includes the E protein, which is presumed to interact with the host cell receptor during virion attachment. The 30nm nucleocapsidis surrounded by a lipid bilayer with embedded viral envelop and membrane proteins and are consists of capsid and genomic RNA. This includes an ≈11-kb RNA genome complexed with the capsid C protein. Virion penetration is believed to occur by means of receptor-mediated endocytosis and is followed by uncoating and release of the genome RNA that functions as messenger RNA. The single long ORF of the uncoated viral genome first is translated by the host cell protein synthesizing machinery into a large viral polyprotein. Proteolytic processing of the viral polyprotein precursor occurs by a pathway involving viral and cellular protease activities to generate mature viral structural (E, C, and M) and nonstructural (NS) proteins, including the NS3 serine protease and NS5 RNA polymerase. In addition to its initial role as mRNA, the positive-stranded genome RNA

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