Retroviruses

Front 1

Overview of all of the RNA viruses by category and morphology:

Back 1

Front 2

RETROVIRIDAE KEY POINTS:
-structure
-polarity
-unique traits
-two genera

Back 2

Enveloped, icosahedral nucleocapsid

Genome consists of TWO COPIES of positive-sense RNA

Virion carries RNA-dependent DNA polymerase (Reverse Transcriptase), other enzymes and tRNA.

Replication proceeds through a DNA intermediate (provirus)

Two genera of human interest:
- Oncovirinae (HTLV-1, HTLV-2, HTLV-5)
- Lentivirinae (HIV-1, HIV-2)

Front 3

Do RNA tumor viruses cause cancer?

Back 3

No-- they are risk factors for cancer, though.

Front 4

What kind of virus is this and what types?

Back 4

Retroviruses.
C type is HTLV
D type is HIV

Front 5

Back 5

top: C-type (HTLV)
bottom: D-type (HIV)

Front 6

Describe the structure of Retroviruses:
-RNA #
-important enzymes
-glycoproteins

Back 6

-Diploid RNA
-Associated with reverse transcriptase, integrase, and a protease
-GlycoPROs: gp120 for attachment; gp41 involved in membrane fusion

Front 7

∆ b/t oncoviruses and lentiviruses in their cytolicity and methods of spread:

Back 7

-Oncoviruses are spread cell to cell, and aren't cytolytic

-HIV spreads cell to cell, is cytolytic, and can travel as a free virus as well.

Front 8

What genes do simple retroviruses have?

Back 8

GAG : internal proteins

ENV: Envelope glycoproteins

POL: Enzymes--Reverse transcriptase, Integrase, Protease

- Long Terminal Repeats are used by viruses to insert their genetic material into the host genomes.

Front 9

Summary of simple retrovirus gene products and their functions:

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Front 10

∆ b/t a simple retrovirus and a complex one?

Back 10

A complex retrovirus has the 3 genes + additional accessory genes.

Front 11

Describe Attachment and Entry of a retrovirus into the host:

Back 11

-Need CD4
-Coreceptor is key for binding (CCR5 on macrophages or CXCR4 on activated T cells).
-Viruses can mutate b/t being T-trophic or macrophage-trophic.

Front 12

Describe the replication of retroviruses:
-what is a key ∆ b/t onco and lenti viruses in this step?

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1) ssDNA formation
2) dsDNA formation
3) insertion into host genome
*oncoviruses stay in this integrated state permanently; don't bud as often
*HIV is cytolytic; more often buds out and moves on.

Front 13

At what steps in replication are key enzymes involved?
-reverse transcriptase
-integrase
-host RNA Polymerase

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Front 14

List the key enzyme acting at each step:

Back 14

Front 15

What do oncoviruses cause?

What are the two mechanisms of oncogenesis in oncoviruses?

Back 15

-Associated with the development of leukemias, sarcomas, and lymphomas.

* Direct or acute transforming retroviruses, which rapidly transform cells and are highly oncogenic [animals]

*Indirect or transactivating retroviruses, which promote uncontrolled cell growth by transctivation of cellular genes; group includes HTLV-1 and HTLV-2 [humans]

Front 16

What do oncogenes encode?
4

Back 16

-Proteins that are involved in growth control and differentiation
-Growth factors
-Growth factor receptors
-Signal transduction proteins
-Transcription factors

Front 17

Key points regarding Human T-lymphotropic virus (HTLV-1):
-what key protein is made by it?
-associated disorders?

Back 17

-It's an Indirect/transactivating retrovirus.

-Can cause human cancer after a long latency period

-Involves viral transcriptional regulator called tax

-Associated with lymphoid malignancies; virus infects CD4 helper T cells.

-Associated with a neurologic disorder (HTLV associated myelopathy/tropical spastic paraparesis; HAM/TSP)

-Transmission is via cell-to-cell contact during exchange of body fluids.

Front 18

HTLV life cycle and spread:

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-Upregulation of tax increases IL-2; which increases CD4 proliferation --> T cell leukemia

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Back 19

Transformed "flower" T cells from HTLV.