Virology And Pathogenesis

Viruses of the Paramyxoviridae family include a number of highly contagious human and animal pathogens, including measles and mumps viruses. NiV is a single-stranded, negative sense nonsegmented RNA virus that is protein encapsidated, helical in shape, and is 120-500 nm in diameter.[6] By electron microscopy, the virus is pleomorphic in appearance and the nucleocapsid has a ''herringbone appearance,'' as seen in Fig. 1.[7] The entire length of the NiV genome is 18,246 nucleotides, which is 12 nucleotides longer than HeV, and demonstrates 70% nucleotide homology in the open reading frames (ORFs) and 44-66% homology in the 5' and 3' noncoding regions with HeV.[2,6] It shows broad tropism for a number of cell lines, as is common for Paramyxoviruses. In culture, the virus infects cells through pH-independent membrane fusion mediated by its F and G glycoproteins, forms syncytia, and the cytopathic effect consists of multinu-cleated giant cells, vacuolation, and apoptosis.[7]

The NiV genome contains multiples of 6 nucleotides conforming to the ''rule of 6'' of other Paramyxovirinae,

Fig. 1 Electron micrograph of Nipah virus. [From Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia.]

thereby allowing for greater efficiency of genome replication.1-6'8-1 Additionally, the genome contains 6 major genes (in order from 3' to 5' end) as summarized in Table 1: N (nucleocapsid), P/V/C (phosphoprotein/V pro-tein/C protein), M (matrix), F (fusion), G (attachment glycoprotein), and L (large polymerase).[9,10] The NiV 3' leader sequence is 55 nucleotides long and is identical to other Paramyxovirinae, and there is a 33-nucleotide trailer at the 5' end. Whereas the 3' leader sequence is nearly identical to HeV, the NiV 5' trailer is significantly longer and differs by 3 nucleotides.[6] The N gene of NiV is 2242 nucleotides long and contains two major predicted ORFs. The larger of the two (1599 nucleotides) encodes for a 532 amino acid protein, and the smaller ORF encodes for a 72 amino acid protein that is not found in the HeV N gene.[10] The ORF of the mRNA for the N gene of NiV shares 78% homology with that of HeV, whereas homology in the nontranslated 5' and 3' regions is 67% and 41%, respectively.[10] The N protein is the most abundant protein in the Nipah virion and has an apparent molecular mass of 58,000 Da.[9] Genomic RNA forms complexes with N to produce the nucleocapsid.

The mRNA for the P/V/C gene of NiV is predicted as 2702 nucleotides and contains ORFs that encode the P, V, and C proteins.[10] The extent of homology of the ORF between NiV and HeV is approximately 70% for the P gene, 88% for the V gene, and 85% for the C gene.[9,10] The P protein is the largest protein encoded by the P/V/C genes of NiV and has a calculated molecular mass of 78,301 Da.[9] C and V proteins may regulate transcription and replication. The V protein is thought to facilitate the evasion of host cell interferon by inactivating interferon signaling by direct inhibition of STAT1 and STAT2, which are interferon-responsive transcription factors.[11]

The mRNA for the M (matrix) gene is predicted at 1359 nucleotides in length and contains an ORF of 1059 nucleotides that encodes a 352 amino acid protein that has a molecular mass of 39,928 Da.[10] The HeV and NiV M proteins are 77.1% homologous and share significant sequence homology with M proteins of morbilliviruses. The ORF of the F gene is 1641 nucleotides in length, and the mRNA for the entire gene is predicted to be 2337 nucleotides. The F protein is thought to be a type I transmembrane protein whose membrane spanning domain occurs at amino acids 489-518 and is synthesized as an inactive precursor (F0) that is cleaved by host proteases forming Fj and F2.[6] The ORF that encodes the putative attachment glycoprotein (G) of NiV is 2543 nucleotides in length and has 83.3% homology with that of HeV.[12] Both the F and G proteins are membrane glycoproteins that mediate viral fusion and attachment to host cells. Both the G and F proteins are targets for host neutralizing antibodies, suggesting a potential role for the F and G

proteins as vaccine constructs.[12]

Nipah virus demonstrates significant tropism for endothelial and neuronal cells in humans and for neuronal and respiratory tract cells in pigs.[13] It is not fully known where initial replication occurs, but it is assumed that either lymphoid or respiratory sites are involved as with other Paramyxoviruses such as measles virus.[2] Viremia probably spreads the virus to other tissues. The endothe-lium may represent a secondary site of viral replication. Vasculitis is a key element in the pathogenesis of NiV infection, and the presence of viral antigens within endo-thelial and smooth cells supports the importance of vascular tropism in the pathogenesis of the infection.

Wong et al.[14] have recently reported an animal model of NiV infection that appears similar to acute infection in humans. In this study, golden hamsters (Mesocricetus auratus) were challenged either intraperitoneally or intranasally, and the investigators evaluated the clinical course, transmission of NiV to uninfected animals housed with challenged animals, and pathology in infected animals. Uninfected animals housed with challenged animals did not develop clinical signs or seroconversion.

Table l Molecular characterization of nipah virus
Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook


Post a comment