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Flashcards in Viruses and Cancer Deck (39):

Development of Adult T Cell Leukemia

HTLV-1 encodes Tax, which is an growth-promoting gene that causes replication and proliferation of the host cell 

As T Cells proliferate, immune cells begin to recognize Tax

Normally, this is enough to prevent cancer, but can lead to cancer in immunocompromised 


B Cell Lymphoma Immunotherapy

Rituximab as a monoclonal antibody that targets CD 20



Progression of EBV and KSHV to Cancer

Disease is caused by unregulated proliferation of infected cells and is associated with immunosuppression 

Diseases are associated with latency - viral genes are transcribed during this period (compared to HSV where no genes are transcribed) 


Burkitt's Lymphoma

Unexplained swollen painless lymph nodes, may have expanding abdominal mass

Endemic to Africa

Malaria is a cofactor for development of Burkitt Lymphoma

Involves dysregulated form of c-MYC from t(8,14) translocation 


Diagnosis and Treatment of Merkel Cell Carcinoma

Tumor cells express Cytokeratin 20 and MCV Large T

Treat with surgical excision, lymph node surgery, ratiation, and chemotherapy

Treat the Tumor, not the virus! 


Merkel Cell Virus

Polyoma Virus that encodes Large T oncoprotein 

Causes Merkel Cell Carcinoma, a rare neuroendocrine carcinoma of the skin that affects mostly older white men


Tropism of EBV and KSHV

EBV: B cells and epithelial cells

KSHV: endothelial, epithelial, and B cells (much less prevalent in population than EBV)


Pap Smear

Includes Nuclear stain, Orange keratin stain, and light green stain for Cytoplasm of other cells

A normal pap smear should show no keratin, and cells should have a small, dense nucleus 

Abnormal pap smear shows keritinization, dyskaryosis, microvascularization, and perinuclear clearing 


Low risk HPV

The E6 and E7 proteins of low-risk HPV do not suppress activity of p53 and Rb


How does HPV lead to cancer?

E6 and E7 are only expressed when virus integrates into genome

This is because the Circular DNA of HPV breaks at the center of the L1 gene and E2 gene

E2 protein blocks transcription of E6 and E7

Lack of L1 helps virus evade immunity 

0.8% of infected people develop cancer 


Characteristics of human tumor viruses

  1. High rates of infection, low rates of cancer
  2. Cancer occurs many years after infection
  3. Virus causes initiation events and allows cells to outlive their lifespan or removes cell cycle breaks
  4. Viral genomes become integrated into host cell genome
  5. Often activate signaling proteins or express oncogenes
  6. Patient's immune response plays a role - chronic immune response in regerative tissue 


EBV and Lymphomas

Burkitt's Lymphoma - Common in African Children, t(8,14)

CNS Lymphomas - 100% caused by EBV, associated with AIDS

Hodgkin's Disease - Hispanic, men, HIV+


Important proteins in HPV

L1 Protein - encodes the capsid - target for vaccine and new PCR diagnostics

E6 - inactivates p53

E7 - inactivates Rb


Where does HPV preferentially infect?

Narrow transformation zone at transition between columnar epithelium and squamous epithelium 

This transition occurs in cervix and rectum 


HPV Vaccine

(strains, approved for, protection percent)

Protects against HPV 6, 11, 16, and 18

Vaccine is against L1 Proteins

Approved for women and men age 9-26

Protects against 90% of genital warts and 70% of cervical cancer

Newer vaccine protects against 9 strains and covers 90% of cervical cancer 


Pros and Cons of PCR test for HPV

Pros: Cheaper and easier

Cons: Doesn't detect non-HPV Cervical Cancer (about 10%), doesn't identify later stage of virus after it integrates (no more L1 protein)


Primary Effusion Lymphoma

Usually occurs in people who are both EBV and KHSV positive 

Lymphoma of pleural cavity

Highly resistant to therapy 

Treat with chemotherapy - not HAART 


HPV and Oral Cancer

  • Commonly affects males
  • HPV-related oropharyngeal cancers have better prognosis than other forms because it's more responsive to treatment
  • Most commonly caused by HPV 16


Diseases of EBV

  1. Oral Hairy Leukoplakia
  2. Nasopharyngeal Carcinoma
  3. EBV Mononucleosis (characterized by heterophile antibodies)
  4. Bukitt's lumphoma
  5. Hodgkin's Lymphoma


Why does HIV lead to cancer if it just affects CD 4 cells? 

CD 4 cells have a required co-signal to efficiently activate CD 8 cells

If CD 8 cells are not efficiently activated, they cannot stop cancer 

This is why you can treat many cancers by fixing the underlying immunocompromised state 


Inflammation and Cancer

Hepatitis B and Hepatitis C cause chronic inflammation in liver cells, which generates reactive oxygen species and constant regeneration

Eventually this may lead to mutations that accumulate and cause cancer 


How EBV transforms B Cells

Normal B cells require T Cell co-signal in order to proliferate; and they commit apotposis when they stop receiving this signal (CD 40 on B Cell binds CD 40L on T Cell)

EBV Latency proteins induce antigen-independent B Cell proliferation and differentiation without the need for co-stimulatory signal 

This results in large proliferation of B Cells, which can lead to cancer. Normally this proliferation is controlled by killer T cells, but can be dysregulated in immunocompromised 


Why don't viruses that actively replicate cause cancer?

Active viral replication causes cell lysis, which prevents the cell from becoming cancerous 


Oral Hairy Leukoplakia

White plaque on tongue that cannot be scraped off

Caused by EBV in immunocompromised 


Treatment for Lymphomas

Treating the HIV can treat the cancer

Use HAART to restore immune response 


Name some ways viruses can cause a cell to progress towards cancer

  1. Damage to DNA
  2. Impaired Apoptosis (p53)
  3. Inactivation of tumor suppressor genes (Rb)
  4. Activation of growth-promoting oncogenes 
  5. Altered gene products (proteins); abnormal structural and regulatory proteins 


Viral proteins that attack Rb

E7 (papilloma viruses) and Large T (polyoma viruses)


EBV Nasopharyngeal Carcinoma

Rare in US; Common in China/Taiwan

Difficult to diagnose


Ways to screen for cancer caused by HPV

  1. Pap Smear 
  2. PCR for L1 protein 



(disease, infectivity)

Causes Adult T Cell Leukemia in 1-4% of people it infects; cancer occurs 20-30 years after infection 

HTLV-1 genome is integrated with host genome


Enzymes that activate antiviral drugs in Alpha Herpes Virus vs Beta Herpes Viruses and CMV

Alpha: Thymidine Kinase

Beta and CMV: Phosphotransferase


Risk factors for Merkel Cell Carcinoma

UV A exposure

Weakened immune system (HIV, organ transplant)

White males over 50


proteins that attack p53

E6 (papilloma viruses) and Large T (polyoma viruses)


Differences between Papilloma and Polyoma Viruses

The differences are the oncogenic proteins;

Papilloma Viruses contain E6 and E7

Polyoma Viruses contain Large T


Why it's important for viruses to inactivate p53

Viral DNA looks like damaged DNA to the cell, so inactivating p53 helps prevents Apoptosis and/or removal of viral DNA



Kaposi's Sarcoma - AIDS defining malignancy 

Multicentric neoplasm consisting of multiple vascular nodules in skin

Treated with HAART 


Know the types of Papilloma Virus and what diseases they cause 

Types 1 and 2 - Common warts

Types 6 and 11 - Genital warts

Types 16 and 18 - Cervical Cancer 



Protein found on Killer T cells that makes their activation less likely

Many tumors express a PD-1 ligand to prevent Cytotoxic Cell Destruction 

New Monoclonal Antibodies (Avelumab and Pembrolizumab) target this receptor to allow T Cells to kill cancer 


Percent of human cancers related to viruses

up to 35%