Friday, 20 March 2015

KNOW EVERYTHING ABOUT EBOLA

Ebolavirus

Ebolavirus cycle

buddattachfusionSTATikketranscriptionrepliImage Map

REPLICATION

CYTOPLASMIC
  1. Attachment to host receptors through GP glycoprotein mediates is endocytosed into vesicles in the host cell. Host DC-SIGN and DC-SIGNR play a role in virion attachment.
  2. The virion enters early endosomes by Macropinocytosis.
  3. In some culture cells, GP glycoprotein can be processed by host Cathepsin L and Cathepsin B into 19kDa GP1. But this processing is not happening in all cells or for all ebolavirus. 19kDA GP1 interacts with host NPC1, which is highly expressed in dendritic cells.
  4. Fusion of virus membrane with the vesicle membrane is triggered by either low pH or NPC1 binding. The ribonucleocapsid is then released into the cytoplasm.
  5. Sequential transcription, viral mRNAs are capped and polyadenylated by polymerase stuttering in the cytoplasm.
  6. Replication presumably starts when enough nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.
  7. The ribonucleocapsid interacts with the matrix protein, and buds via the host ESCRT complexes from the plasma membrane, releasing the virion 

    Molecular biology

    Filamentous 970 nm long for Ebolavirus. Diameter is about 80nm.

    GENOME

    Negative-stranded RNA linear genome, about 18-19 kb in size. Encodes for seven proteins.

    GENE EXPRESSION

    The viral RNA dependent RNA polymerase binds the encapsidated genome at the leader region, then sequentially transcribes each genes by recognizing start and stop signals flanking viral genes. mRNAs are capped and polyadenylated by the L protein during synthesis.
    The primary product of the unedited transcript of GP gene yields a smaller non-structural glycoprotein sGP which is efficiently secreted from infected cells. RNA editing allows expression of full-length GP.

    REPLICATION

    CYTOPLASMIC
    1. Attachment to host receptors through GP glycoprotein mediates is endocytosed into vesicles in the host cell. Host DC-SIGN and DC-SIGNR play a role in virion attachment.
    2. The virion enters early endosomes by Macropinocytosis.
    3. In some culture cells, GP glycoprotein can be processed by host Cathepsin L andCathepsin B into 19kDa GP1. But this processing is not happening in all cells or for all ebolavirus. 19kDA GP1 interacts with host NPC1, which is highly expressed in dendritic cells.
    4. Fusion of virus membrane with the vesicle membrane is triggered by either low pH orNPC1 binding. The ribonucleocapsid is then released into the cytoplasm.
    5. Sequential transcription, viral mRNAs are capped and polyadenylated by polymerase stuttering in the cytoplasm.
    6. Replication presumably starts when enough nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.
    7. The ribonucleocapsid interacts with the matrix protein, and buds via the host ESCRTcomplexes from the plasma membrane, releasing the virion .

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