Papillomaviridae

VIRION

Non-enveloped. Small, icosahedral, about 60 nm in size. A single molecule of circular dsDNA is contained within the T=7 icosahedral capsid, which is composed of 72 pentamers.

GENOME

Circular dsDNA, about 8 kb in size, associated with cellular histones in a chromatin-like complex.
On rare non-specific recombination, the viral genome can be integrated in host chromosome. This inactivates the integrated virus but can gives the host cell a replicative advantage sometimes leading to malignant tumours.

GENE EXPRESSION

Only one strand of the genome is transcribed and yield two classes of proteins expressed by alternative splicing :
a) Early Proteins: non-structural regulatory proteins (E1-E7).
b) Late Proteins: the structural proteins L1 and L2.

REPLICATION

NUCLEAR

Replication is divided in two distinct steps that are linked to the differentiation state of the host epithelial cell:

a) The plasmid replication takes place in the basal squamous epithelial cells. It corresponds to viral DNA replication in synchrony with the host cell chromosome in order to ensures an average of one viral genome per basal cell.

  1. Attachment of the viral proteins to host receptors mediates endocytosis into vesicles in the basal squamous epithelial cell.
  2. Transport to the nucleus and uncoating of the viral DNA.
  3. Early-region transcription and translation of the early proteins.
  4. Steady-state viral DNA nuclear replication. Requires the origin of DNA replication in cis and the viral E1 and E2 proteins in trans.

b) The vegetative replication, which occurs in differentiated keratinocytes. In these cells, which no longer undergo cellular DNA synthesis, there is a burst of viral DNA synthesis with active production of virions.

  1. Vegetative viral DNA synthesis.
  2. Transcription of the late region.
  3. Capsid proteins L1 and L2 synthesis.
  4. Nuclear capsid assembly and release of viruses.

Host-virus interaction

Adaptive immune response inhibition

The E5 protein in papillomaviruses plays a role in the inhibition of host adaptive response by down-regulating the cell surface expression of MHC class I .

Apoptosis modulation

The oncogenic type of human papillomaviruses (HPVs) E6 has among its functions the ability to prevent apoptosis of infected cells through its binding to FADD and caspase 8 .

Cell-cycle modulation

The E7 protein from the high-risk HPV type 18 forms a complex with cyclin E and regulates transit from G1 to S. HPV61 E7 binds cyclin A, which regulates transit through the S and G2/M phases of the cell cycle .

Innate immune response inhibition

Papillomaviruses inhibits the cascade leading to production of interferon-beta by targeting the IRF3 cellular protein. Indeed, The viral E6 protein is able to interact with host IRF3 and inhibits its transcriptional activity .

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