1021 - Papilloma and Herpes Viruses

Question 1

How does HPV cause cancer?

Answer 1

HPV’s method of proliferation relies on inducing cell division. While HPV is replicating, some of the viral genome can become coded into the cell genome. This DNA can thus persist effectively as an oncogene, even if the virus is able to be cleared by the body. Thus, the cell can continue to divide and proliferate, leading to malignancy.

Question 2

Explain the basis of the cervical cancer vaccine in terms of molecular biology and immunology.

Answer 2

L1 is the major capsid protein of HPV, and pentamers composed of L1 are able to self-assemble into a ‘virus-like particle’ - essentially the capsid without the genetic code - looks like a virus but nothing inside. As a result, the VLPs generate a significant immune response with no risk of infection, provided that recipients are HPV-negative at the time of vaccination. Strictly speaking, it is an anti-viral, not an anti-cancer vaccine.

Question 3

What are the five main herpes viruses? What diseases do they cause?

Answer 3

Herpes Simplex 1 - Cold Sores
Herpes Simplex 2 - Genital herpres (though these are not tropisms - mucus membrane is a mucus membrane, just found there more commonly)
Varicella-zoster virus - Chickenpox and shingles
Cytomegalovirus - Generally asymptomatic, but severe infections in-utero (birth defects) and immunocompromised.
Epstein-Barr virus - Glandular fever, and several cancers.

Question 4

What is latency? How is it important to herpes viruses?

Answer 4

Latency describes the ability of the virus to lay dormant - without causing active infection or generating an immune response - for years or decades - before reactivating, with or without symptoms. It is an ideal evolutionary strategy, as it means that the virus is not cleared by the immune system, and does not kill its host, but is able to reactivate and spread at appropriate times. Asymptomatic reactivation allows the virus to spread without the host’s knowledge.

Question 5

What are the five main herpes viruses? How do each exploit latency?

Answer 5

HSV 1&2 - Latent in nerve cells, with re-activation leading to virus shedding with or without symptoms.
Varicella Zoster - Latency in sensory neurons, reactivation leads to neural and skin infection in that dermatome, with associated virus shedding.
Cytomegalovirus - Latency in myeloid progenitors in bone marrow, reactivation is usually asymptomatic but allows for virus shedding.
EBV - Latency in B-lymphocytes and some epithelial cells. Reactivation is usually asymptomatic.