DNA Viruses and Polyomaviruses

Question 1

Requirements

Answer 1

• Template to copy
• DDDP (either host of viral encoded)
• Presence of a free 3’ -OH to which elongation can occur
• RNA primer to provide the initial 3’ -OH (This has to be done by an RNA polymerase since no DNA polymerases are capable of initiating DNA replication without a primer)
• DNA synthesis occurs only in 5’ –> 3’ direction, so when copying a double stranded template one of the strands must be synthesized discontinuously
• DNA ligase is required to seal the discontinuously synthesized DNA strands bringing a 5’ phosphate together with a 3’ -OH to form a phsophodiester bond
• Origin of replication
• During early and late phases of replication DDRP are used for transcription of genes into mRNA with the exception of poxviruses that replicate in the cytoplasm so they utilize host DDRP II present in the nucleus
• Poxviruses must encode/carry a gene for DDRP into the infected cell for initial early transcription, so they have an vision associated DDRP
• Early transcriptional/translational processes are involved with DNA replication while late processes are involved with synthesis of structural components of viruses

Question 2

DNA viruses

Answer 2

Vision –> nucleus (transcription: mRNA production) –> cytoplasm (translation into proteins) –> Immediate early and early/structural proteins some with regulatory functions –> from immediate early/early to regulatory proteins and enzyme for DNA synthesis

Question 3

Polyomaviruses (SV 40)

Answer 3

VP1-4 = capsid proteins
LT(Large T antigen) = drives process, makes this oncogenic by causing cell to go under constant replication, integration, and can become persistent

Question 4

Human Polyomaviruses

Answer 4

JC and BK discovered in 1971; virus infection occurs early in life and establishes a persistent infection;generally benign infection; in immunosuppressed patients and MS patients with natalizumab develop PML and fatal CNS disease caused by JC; BK contributes to PVAN in renal transplant patients and in patients with hemorrhagic cystitis receiving hematopoietic stem cell transplants

Question 5

Merkel Cell Carcinoma

Answer 5

• Defined in 1972 as a rare aggressive skin cancer
• Higher incidence in immunosuppressed patients of organ transplants and in AIDS patients
• Virus genome is integrated and in most cases mutations in large T antigen that prevent virus replication but preserve expression of oncogenic proteins