zika virus virology

Zika virology--Family

Zika virus belongs to Flaviviridae family which contains some of the most clinically important arboviruses. Epidemiologically, the arthropod-borne flaviviruses can be divided into mosquito-borne and tick-borne viruses. Clinically, the most prominent syndromes caused by flaviviruses are undifferentiated febrile illnesses (often presenting as a fever with rash syndrome), central nervous system infection (especially encephalitis), visceral involvement, and haemorrhagic fever.

Zika virology—Structure and antigens

Flaviviruses are enveloped, single-stranded, positive sense RNA viruses with 50nm in size. Full length of genome is nearly 10.5 to 11 kbp. A polyprotein with more than 3000 amino acids is produced by the genome. To be mature, the polyprotein will be cleaved into three structural and seven non-structural proteins.

Proteins Functions Possible effects on hosts
C RNA binding to form the nucleocapsid.  
prM, M Stabilization, assisting the folding and secretion of E protein. Antibodies towards prM enhances infectivity of immature virions, could be involved in pathogenesis of severe dengue in secondary infections.
E Receptor binding, membrane fusion.  
NS1 RNA replication. Localization to host cell surface and secreted extracellularly; modulates signalling of innate immune system, possible damages to platelets and endothelial cells through anti-NS1 antibodies, antagonizes C4 complement.
NS2A RNA synthesis and viral assembly. Interferon antagonist, induces host cell apoptosis.
NS2B Complexes with NS3 to function as serine protease.  
NS3 Complexes with NS2B to function as serine protease; possess RNA helicase and triphosphatasae activities. Induces apoptosis of host cells, modulates host microRNA,one of the targets of cytotoxic T cell response.
NS4A RNA replication. Blocks type I interferon signalling, induces autophagy and protects host cells from death during infection.
NS4B RNA replication. Blocks type I interferon signalling and RNA interference, modulator of stress granules in host cells.
NS5 Methytransferase and RNA guanylyltransferaseactivities; capping and synthesis of RNA;RNA-dependent RNA polymerase. Blocks type I interferon signalling.

But, this conclusion is based on previous studies on clinically flaviviruses. For example, dengue virus, west nile virus, yellow fever virus. Whether it is generalized to Zika virus is still need to research.
In 1950s, isolation of zika virus from humans was reported. The genomes of those three human isolates of zika virus are 10.676 bp, which is comparable to other members of Flaviviridae.

Zika virology—vector and host receptor

Typically, Zika virus Zika virus is transmitted to a bitten human host after skin injection of a mixture of insect saliva, virus, and blood components from the most recent feeding during female mosquito blood meals. Probability of viral particle transmission is related to the volume of fluid held in the proboscis from a prior blood meal, viral replication levels and volume of insect salivary glands, and the viral infectious titer of the preceding host. Zika infection of the recipient host requires viral envelope protein binding and particle uptake into susceptible cells, is mediated by specific receptors which include DC-SIGN, AXL, Tyro3, and TIM-1, and triggers transcriptional activation of Toll-like receptor 3 (TLR3), RIG-I, MDA5, interferon stimulated genes including OAS2, ISG15, and MX1, and beta interferon.

Zika virology—Infection

The infection and host response cascade triggered by initial infection with Zika virus has yet to be characterized. Human infection by dengue provides one of the most classic examples of antibody dependent enhancement of disease by pre-existing non-neutralizing antibody, resulting in dengue hemorrhagic fever [107, 108]. The potential role of antibody dependent enhancement (ADE) of Zika infection and disease has not been examined.The duration of viremia, infectivity, and persistence of Zika virus, is not known for either post-partum or intrauterine infection. Nor is the route of fetal infection, or the degree of neurotropism. Related flaviviruses may cause persistent infection despite the presence of serum antibodies.

Zika virology—immunoinformatic analysi

Analysis of the envelope protein of Zika, from Brazilian Zika SPH2015 (KU321639), indicates predicted B and T cell epitopes in peptides that are consistent to those reported for dengue, YFYF and Japanese encephalitis. The envelope Domain II B cell epitope, to which much dengue non-neutralizing cross reaction is attributed, is also conserved also in Zika, consistent with prior field observations of cross reactivity with dengue and YF. Domain III of the Zika envelope protein, likely the main specific neutralizing domain, is distinct from recent Brazilian dengue isolates and a recent Peruvian YF isolate (GQ379163), 76% of possible major histocompatibility complex class (MHC) I and MHC II binding peptides and potential B cell linear epitopes are unique to Zika.

Zika virus virology related refernces

1, Marina Basarab specialty registrar. et al .Zika virus. BMJ 2016; 352:i1049 doi: 10.1136/bmj.i1049
2, Pinto Júnior VL, et al. Zika virus: a review to clinicians, Acta Med Port 2015 Nov-Dec;28(6):760-765
3, L Zammarchi, et al.Zika virus infection in a traveler returning to Europe from Brazil, March 2015
4, Arturo Galindo-Fraga, et al. Zika virus: A new epidemic on our doorstep. Rev Inves Clin.2015, 67: 329-32