HPV Presenation

The Human Papilloma Virus and Its Life Cycle

Presentation by: Sulav Acharya

Introduction• Papilloma Viruses warts ( papillomas ) in

variety of higher vertibrates.• Human pappilomaviruses cervical cancer and

other epithelial tumours.• Cause sexually transmitted disease.• In cervical cancer ,HPV DNA more than 90

percent cases.• More than 120 types of HPV have been identified.

Virion Structure

• Small, non enveloped, icosahedral DNA viruses

• replicate in nucleus of squamous epithelial cells.

• 52-55 nm diameter, DNA about 8000 bp,• Spherical protein coat or capsid composed of

72 capsomers.

Figure 1. The genome organization of HPV16

Early promoter

Late promoter

E1E2E4E5E6E7

L1L2

Structural proteins

Non-structural proteins

P97 = Early promoterP670= Late promoterAE = Early poly (A) signalAL = Late poly (A) signal

Long control region

HPV Gene Function• E1 Viral genome replication with helicase/ ATPase

activity.• E2- is a Transcription factor transactivation and

transrepression.• E6 and E7 Reactivation of cellular replication

mechanism,proliferation,immortalization,inhibition of apoptosis, maintenance of viral genome.

• E4 asscociated with cytokeratins to destabalize the cytokeratin network and aid in viral release at the epithelial cell layer surface, though primary function still unknown.

• E5 possibly involved in proliferation and /or inhibition of apoptosis.

• L1 Major Capsid Protein• L2 Minor Capsid Protein

HPV Life CycleHPVs Damaged areas of the

epithelium

Eating, drinking and est. Infect the basal

cell

Heparan sulfate proteoglycan recepter

Infection and Uncoating

• HPV invade damaged areas of the epithelium an infect basal cells.

• Controversy cell surface receptor so that Virus gets attached to cell.

• Heparin Sulphate and endocytosis of clathrin coated vesicles attachment.

• Disruption of intracapsomeric disulphide bonds so virus enters the DNA nucleus

Genome maintenance• Low copy number episome basal cells of the

epithelium.• E1 and E2 proteins maintain the viral DNA as

an episome and facilate correct segregation of genomes during cell division.

• Finally suggested that expression of E1 and E2 is sufficient for basal maintenance of viral episomes.

Proliferative Phase• In uninfected epithelium, basal cells exit cell cycle

after migrating to suprabasal cell layers and undergo process of terminal differentiation.

• In Viral infection E7 and E6 expressed, therefore restraint on cell cycle progression is abolished and normal terminal differentiation is retarded.

• E7 associates with pocket protein family such as pRb.

• pRb- negative regualtor of cell cycle prevents S-phase entry by association with the E2F family of transcription factors.

Cont……..• E7 binding to pRb displaces E2F leads to the

protein necessary for DNA replication.• E7 in cell proliferation histone deacetylases,

components of Ap-1 and the cyclin dependent kinase inhibitor p21 and p27.

• The Viral E6 protein associates with p53, and inactivation of p53 mediated growth suppression and apoptosis takes place.

• E6 predisposing factor for cervical cancer stimulate cell proliferation of E7 which develops metastatic tumours by disrupting normal cell adhesion.

Genome Amplification• Papilloma virus amplify to produce infectious

virions.• Occours mid or upper epithelial layers and

increase the activity of late promoter.• Late promoter resides in E7 ORF increase

expression of proteins involved in Viral DNA replication.

• Encode 2 structural proteins in upper layer of infected tissue.

• L1 Major coat protein express after L2 which assemble the infectious particle in upper layer.

• L2 Minor coat protein that express E4.

Virus Synthesis