Retroviruses, AIDS, and Tumor viruses

Question 1

Retroviruses are a large and diverse group of viruses from the family ___. Name the two subfamilies.

Answer 1

Family: Retroviridae
Subfamilies: Orthoretroviridae (associated with human disease)
Spumaviridase (not associated with human disease)

Question 2

Avian leukosis sarcoma virus (ASLV), Rous sarcoma virus (RSV)

Answer 2

Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Alpharetrovirus
Genome: (+) ssRNA

Question 3

Mouse mammary tumor virus (MMTV)

Answer 3

Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Betaretrovirus
Genome: (+) ssRNA

Question 4

Murine luekimia virus (MLV)

Answer 4

Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Gammaretrovirus
Genome (+) ssRNA

Question 5

HTLV-1, HTLV-2, HTLV-5

Answer 5

Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Deltaretrovirus
Genome: (+) ssRNA

Question 6

HIV-1, HIV-2

Answer 6

Family: Retroviridae
Subfamily: Orthoretroviridae
Genus: Lentivirus
Genome (+) ssRNA

Question 7

Describe retrovirus biology

Answer 7

• Genome is (+) ssRNA, but it has two identical copies.
• ***Diploid ssRNA replicates in the nucleus where it makes a DNA copy of itself and then integrate inserts the genome into the host DNA. From this you get transcripts of RNA which will be packaged to infect new cells.
• ssRNA -> dsDNA
• Enveloped with proteins
  
  • GP120 and GP141 are associated with attachment and are also associated with resistance.
• Contain reverse transcriptase, and protease
• integrate helps insert the virus genome into host DNA

Question 8

Slow Retroviruses

Answer 8

• Ex. Leukemia virus
• Effect is like high level mutagenesis
• Eventually results in tumorigenesis

Question 9

Cytopathic Retroviruses

Answer 9

• Minority of retroviruses carry cytopathic genes

- These cause tissue damage directly

Question 10

Acute Transforming Viruses

Answer 10

• Induce rapid tumor formation
• Carry host genes - mitogenic or antiapoptotic
• Often replication defective because host gene replaces an essential gene

Question 11

Human T-cell Leukemia Virus (HTLV)

Answer 11

• 4 different types (1,2,3,4) and type 1 is the one most often associated with humans
• deltaretrovirus
  Transmission: Person to person (mother to child via breastfeeding, sharing needles, blood transfusions, sexual transmission)
• Disease: causes adult T-cell lymphoma/leukemia (ATLL) following mucosal exposure. Has a latent period of up to 30-50 years
  
  • infects memory T-cells.
  • Antigen activation triggers transcription of provirus.
  • Virus “tax” protein and others stimulate cell proliferation
• Can also cause HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP)
  
  • Infected T cells enter the central nervous system where the activate astrocytes and microglial cells. They recruit inflammatory cells and can cause further tissue damage.
  • onset is usually 3 years after infection. Starts with bladder control issues and progresses to lower back pain , weakness or stiffness in hips or knees as well as ED.
• Prevention: Eliminate breast feeding in infected mothers and increase screening for blood products.
• Treatment: ATLL - treat the lymphoma/leukemia with chemotherapy regardless of the HTLV infection
  
  • HAM/TSP - use corticosteroids, interferon yields temporary ref lief of symptoms.

Question 12

Human Immunodeficiency Virus (HIV)

Answer 12

• Two types ( type 1 and 2)
• Sexual transmission is primary route of spread, but can be spread from mother to child, can also be spread through needle sharing
• Latent period of 6 months to 25 years
• Targets and replicates in memory T-cells, and the infection is cytopathic for these cells
  Common opportunistic infections: Candida, Coccidiomycosis, Cryptococcus, Cytomegalovirus, Kaposi Sarcoma, Tuberculosis, Toxoplasmosis
  Treatment: No vaccine, but antiviral treatments help slow the pace of disease
• Nucleoside reverse transcriptase inhibitors (NTI) ex. Azidothymidine (AZT)
• Protease inhibitors ex. ritonavir
• Non-nucleoside RT inhibitors (NNRTI) ex. efavirenz

Question 13

Retrovirus Summary

Answer 13

• Enveloped
• Diploid (+)ssRNA genome
• Reverse transcription and integration into host DNA
• Often transmitted sexually, blood transfusions, and by intravenous drug use
• Disease progression is often slow (years)
• Significant cause of certain types of cancer

Question 14

What 3 viral genes are absolutely required for replication of retroviruses?

Answer 14

• Reverse transcriptase (pol)
• Genes for replication of the core and capsid (gag)
• Genes encoding for the glycoprotein spikes on envelope (env)

Question 15

Most retroviruses are defective. Under what conditions are replication defective retroviruses able to replicate?

Answer 15

They can still replicate with the assistance of a helper virus. The helper viruses supply non-defective genes to replace the defective ones.

Question 16

Which is the only RNA virus group that is associated with uncontrolled cell growth or malignancy? What ways do they cause cancer?

Answer 16

• Retroviruses are the only RNA virus group associated with cancer growth.
  1. Transcription controls from the viral genome are inserted adjacent to a host proto-oncogene, turning on the cancer causing gene
  2. Retroviruses with oncogenes in their genome insert the gene adjacent to a host cell promoter, turning on the viral oncogene