• Zika ORF, AAV and Adenovirus


    What is Zika?

    Zika virus (ZKV) is a single-stranded RNA (ssRNA(+)) virus of the Flaviviridae genus. Other members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Further environmental as well as demographic considerations propose that novel or known flaviviruses will likely re-emerge in the future. Nonetheless, it was not until recently that flaviviruses have been considered interesting candidates for drug design. The flaviviral replication complex presents as a very promising target for development of antiviral compounds. Read more about Zika.

    Study the function of Zika virus (ZKV)

    14 ZKV open reading frames (ORFs) as plasmid DNA, AAV, adenovirus

    ● Non-infectious

    ● Used individually or as a group

    ● Works with cells or for in vivo research purposes

    Zika Virus in plasmid DNA, AAV, adenovirus

    Zika Virus Polyprotein diagram

     

    ZIKA polyprotein
    ancC
    C
    preM
    pr
    M
    E
    NS1
    NS2A
    NS2B
    NS3
    NS4A
    2K
    NS4B
    NS5

    Zika Virus Background

    The genome of the ZKV encodes 14 open reading frames (ORFs). The research of ZKV function and the development of ZKV vaccine requires in-depth understanding of the function of each ORF on ZKV. The virion is enveloped, spherical, and about 50 nm in diameter. The surface proteins are arranged in an icosahedral-like symmetry. ZKV encodes a large polyprotein precursor. This precursor is co- and post-translationally processed by viral and cellular proteases into three structural proteins; building the capsid, and seven non-structural proteins involved in virus replication.

    Zika Key facts

    ● Zika virus disease is caused by a virus transmitted primarily by the Aedes mosquitoes.

    ● Persons with Zika virus disease may have symptoms which include mild fever, skin rash, conjunctivitis, muscle and joint pain, malaise or headache. Such symptoms normally last for 2-7 days.

    ● Scientific consensus states that Zika virus is the cause of microcephaly and Guillain-Barré syndrome. Links to other neurological complications have also been investigated.

    ● Learn more about Zika at CDC and WHO

    Zika gene expression

    Zika virion RNA is infectious and serves as the genome and viral messenger RNA. The entire genome is translated into a 3,419 aa long polyprotein, which is processed co- and post-translationally by both host and viral proteases.

    Zika replication

    ZKV replication occurs in the cytoplasm in mammals, and nuclear in insects.

    The following is ZKV replication:

    ● 1 - Attachment of the viral envelope protein E to host receptors. Mediates internalization into host cell by apoptotic mimicry.

    ● 2 - Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm.

    ● 3 - The genomic ssRNA(+) is translated into a polyprotein, which is cleaved into all structural and non structural proteins (to yield the replication proteins).

    ● 4 - Replication takes place at the surface of endoplasmic reticulum in cytoplasmic viral factories. A dsRNA genome is synthesized from genomic ssRNA(+).

    ● 5 - dsRNA genome is transcribed/replicated thereby providing viral mRNAs/new ssRNA(+) genomes.

    ● 6 - Virus assembly occurs at the endoplasmic reticulum. The virion buds at the endoplasmic reticulum and is transported to the Golgi apparatus.

    ● 7 - The preM protein is cleaved in the Golgi, thereby maturing the virion which is fusion competent.

    ● 8 - Release of new virions via exocytosis.

    It is pertinent to know that although precise details of flavivirus replication have seen significant advances in the past years, numerous aspects remain that are not fully understood.