Zika Virus NS1 ELISA Kit

Zika virus (ZIKV) is a virus of the genus Flavivirus in the family Flaviviridae. Studies have shown that ZIKV is mainly transmitted to humans by Aedes aegypti and Aedes albopictus. ZIKV was first isolated from a monkey in the forests of Uganda in 1947. Initially, no disease caused by ZIKV was discovered until some patients developed Guillain-Barré syndrome after being infected with Zika virus. Guillain-Barré syndrome (GBS) is a serious neurological disorder. Studies have shown that ZIKV infection in pregnant women can cause congenital malformations such as microcephaly and other neurodevelopmental defects in newborns, and can even lead to miscarriage and stillbirth. In mouse models, it can cause testicular damage and ultimately lead to male infertility. In addition, cardiovascular complications, uveitis, acute liver injury and coagulopathies have been associated with ZIKV infection. The ZIKV genome is a single-stranded positive-stranded RNA of approximately 10.7 kb in length. Similar to other flaviviruses, the ZIKV genome contains a single open reading frame (ORF) with 5' and 3' untranslated regions (UTRs) at both ends of the ORF. The ORF encodes a long polyprotein of 3423 amino acids. After translation, the protein is cleaved by host and viral proteases into three structural proteins (capsid protein (C), precursor membrane protein (prM) and envelope protein (E)) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4ANS4B, NS5). The ZIKVE protein consists of four domains: the transmembrane neck region is mainly responsible for membrane anchoring; the remaining B-sheet structures constitute domains I, II, and III. Domain I of the E protein acts as a bridge to connect domains II and III; the top of domain III is a fusion peptide (FL), which participates in the membrane fusion of host cells. For most flaviviruses, domain III may contain potential receptor binding sites and play an important role in membrane fusion. Interestingly, domain I of the ZIKVE protein has only one glycosylation site (N154). Compared with other flaviviruses such as DENV, domain I of the ZIKVE protein has a longer "150 loop" (amino acid residues 145-160), and the glycosylation site just extends from the surface of this loop.

Figure 1. Genomic organization and structure of ZIKV. (Sources: Pierson TC, et al. 2018)

ZIKV NS1 is a relatively conservative nonstructural protein, which consists of 352 amino acids. The molecular weight varies according to the degree of glycosylation, which is about 46-55 kDa. Similar to NS1 of other flaviviruses, ZIKV NS1 dimer is located inside the endoplasmic reticulum cavity of the cell, and can interact with NS4B and NS4A to participate in the formation of the replication complex. In addition, a small part of NS1 dimer is transported to the surface of the cell membrane. Studies have found that NS1 hexamers secreted outside the cell interact with various factors of the host in the form of lipoproteins, causing various disease symptoms. Of course, NS1 secreted outside the cell is highly immunogenic during ZIKV infection and can be used as a biomarker for disease diagnosis. Studies have shown that the difference in NS1 coding sequences is the major genetic factor responsible for the occurrence of different clinical symptoms following infection with different flaviviruses. The life cycle of arboviruses involves virus transfer between vertebrate hosts and arthropod vectors, with vector uptake of the virus from the infected mammal being a critical step in this process. Previous reports suggest that flavivirus NS1, which is released in large quantities in the serum of infected hosts, plays an important role in mosquito uptake of the virus. NS1 may help viruses cross the immune barrier in the mosquito midgut, promote mosquito acquisition of flaviviruses in mammalian hosts, and subsequently increase virus prevalence in mosquitoes. Of the 10 proteins encoded by the ZIKV genome, the first to have a crystal structure is the C-terminal domain of NS1 (NS1_172-352). ZIKV NS1 _172-352 has a long rod-shaped homodimer structure with a length of about 9 nm. One side of the ZIKV NS1 _172-352 homodimer is a ladder-like structure composed of 20 (3-fold sheets, in which each monomer contributes 10 B-fold sheets; the other side of the dimer is an irregular surface formed by multiple loops. Most of the loops between the folds are short, and only between 3.4 and 5 is there a long spaghetti-like loop. There is a highly conserved potential N-glycosylation site at 133-P4. Among the 10 proteins encoded by the ZIKV genome, the first to obtain a crystal structure analysis is the C-terminal domain of NS1 (NS1_172-352). ZIKVNS1_172-352 presents a long rod-shaped homodimer structure with a length of about 9 nm. On one side of the ZIKV NS1_172-352 homodimer is a ladder-like structure composed of 20 β-pleated sheets, in which each monomer contributes 10 β-pleated sheets; on the other side of the dimer is an irregular surface formed by multiple loops. Most of the loops between the folded sheets are short, and only between β4 and β5 there is a long loop similar to spaghetti. There is a highly conserved potential N-glycosylation site on the β3-β4 loop.

In order to prevent and treat ZIKV virus, efficient vaccine development is an effective means. Flavivirus vaccines may cause more severe clinical symptoms due to antibody-dependent enhancement (ADE). Using NS1 as an immunogen to design vaccines can avoid the potential AD E risk of ZIKV vaccines designed based on structural proteins, especially E protein. Since NS1 is not located on the surface of viral particles, NS1 antibodies cannot prevent viral invasion. NS1 antibodies may exert protective effects through the following two different mechanisms: I) Antibodies bind to NS1 on the surface of infected cells and exert protective effects through Fc-mediated complement, ADCC and cell phagocytosis leading to cell death; II) Enhanced response of specific CD8+ T lymphocytes targeting NS1.

Zika NS1
ZIKV NS1
Zika Virus Nonstructural Protein 1
Non-Structural Protein 1 (NS1) of Zika Virus
NS1 Antigen