hpv presenation
TRANSCRIPT
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