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Introduction of Zika Virus

Introduction of ZIKV

Zika virus (ZIKV) belongs to the larger group of arboviruses (arthropod borne viruses). The Aedes genus of mosquitoes is the primary route by which ZIKV is transmitted. Of all the known cases of ZIKV infections, 80% are asymptomatic. The symptoms and signs of patients affected by ZIKV are similar to Dengue virus (DENV) and other viral diseases. The patient may present with fever, body aches, joint pains, fatigue, malaise, and conjunctivitis. Two main lineages have been identified so far from entire genome sequencing namely, the African and the Asian lineages. Further divided into two groups, the African lineage is composed of clusters Uganda and Nigeria. Study demonstrated that single serine to asparagine substitution (S139N) in the viral polyprotein can lead to enhanced infectivity of human and mouse neural progenitor cells (NPCs) by ZIKV. It was also suggested that this functional adaptation can lead to microcephaly in the mouse fetus, and higher mortality in neonatal mice.

A schematic diagram of the ZIKV polyprotein (top panel) and topological arrangement of individual viral proteins (bottom panel). Fig.1 A schematic diagram of the ZIKV polyprotein (top panel) and topological arrangement of individual viral proteins (bottom panel).

Life cycle of the Flaviviridae.Fig.2 Life cycle of the Flaviviridae.

Viral Proteins

ZIKV is a positive-sense RNA that is single-stranded. Only a single polyprotein is encoded by its 10.7 kb genome. It is further cleaved into 10 proteins, three of which are structural and seven of which are non-structural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5).

  1. The capsid (C) protein is a multifunctional protein. It binds to viral RNA in the process of nucleocapsid assembly and plays important roles in virus infection processes by interacting with cellular proteins, modulating cellular metabolism, apoptosis and immune response.
  2. Pre-membrane (prM) protein is a 168-residue long structural protein that shares 42% homology between ZIKV and DENV. In ZIKV, a unique feature is present in prM protein. The first 93 residues serve to protect the protein from premature cleavage. When the intracellular pH drops in response to maturation, the protein is cleaved to allow the virus to mature completely. This unique feature of the prM protein in ZIKV may serve as a target for detection as well as treatment.
  3. Envelope (Env) glycoprotein is a 504-residue long glycoprotein found as homodimers on the viral surface. Env glycoprotein plays a vital role in adhesion to the host cell and is thus central to the virulence of ZIKV. The protein has three β-sheet domains including a centralized amino domain (domain I), a dimerization domain with a fusion sequence (domain II), and a transmembrane immunoglobulin-like domain (domain III).
  4. The structure of NS1 is well conserved across flaviviruses, and IgM serology of NS1 is often used in the diagnosis of flavivirus infection. NS1 may exist as an intracellular monomer, a membrane bound dimer, or a secreted hexamer. Several sites in ZIKV NS1 are unique from other flaviviruses, and it is postulated that these modifications to NS1 are positively selected.
  5. NS2B serves as a cofactor for the activation of NS3.
  6. NS3 contains viral protease and helicase function, both of which are vital for viral replication. The role of the NS3 protease is so important that it is believed the virus will be incapable of replicating if protease inhibitors against NS3 are administered. For this reason, NS3 is a major target being studied for the treatment of ZIKV.
  7. NS4B is a transmembrane protein with two perimembrane domains, one cytosolic domain, and three transmembrane domains. It is responsible for anchoring of the replication complex, evasion of immune response, and various specialized interactions with host cell factors.
  8. NS5 is a 903-residue protein with a methyltransferase on the N-terminal as well as a RNA dependent RNA polymerase domain. It is responsible for the modification of RNA and is essential for viral replication and evolution.

What Creative Biolabs offers?

Creative Biolabs has become a leader of recombinant antibody (rAb) discovery, engineering and manufacturing, providing high quality services to customers in academic and industry fields all over the world. Now we focus on antibody discovery services for ZIKV research. Learn more about our ViroAntibody Discovery Services. Creative Biolabs now provides a variety of ZIKV antibodies targeting the above proteins to meet our clients’ requirements. Customized antibody development services and antibody related virology assays are also available for you. Please submit your specific antibody inquiry to us. We also provide a full comprehensive suite of secondary antibodies and isotype controls to meet your needs. For any questions, please feel free to contact us for more information.

Reference

  1. Yoon, K. J.; et al. Zika-virus-encoded NS2A disrupts mammalian cortical neurogenesis by degrading adherens junction proteins. Cell Stem Cell. 2017, 21(3): 349-358. e6.
  2. Suchetana M, Richard J K, Michael G R. A structural perspective of the flavivirus life cycle. Nat Rev Microbiol. 2005, 3(1):13-22.

All products and services are intended for Research Use Only, and NOT to be used in diagnostic or therapeutic procedures.

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