Yoshimura: Retroviruses

Question 1

Human Retroviruses that cause Immunodeficiency:

Answer 1

HIV-I and HIV-II

Question 2

Human Retroviruses that cause cancer:

Answer 2

HTLV-I and HTLV-II

Question 3

HTLV-I causes:

Why does it only affect adults?

Answer 3

HTLV-I: adult T cell leukemia (takes a long time after infection to cause disease and therefore predominantly affects adults)

Question 4

Tropical Spastic Parapesis is caused by:
Occurs in what %?
Causes:
Effect on mental faculties:

Answer 4

HTLV-I

Occurs in less than 1% of people with this T cell leukemia

Causes weakness in lower body (esp. legs)

Mental faculties remain unaffected

Question 5

How common are HTLV-caused diseases?

HTLV is endemic where?

Answer 5

HTLV-caused diseases are rare with <1% of world-wide population infected.

HTLV is endemic to certain areas of the world; southern Japan, Melanesia, Caribbean, southern USA, and areas in South America and Africa

Question 6

HTLV-II causes:

Answer 6

Hairy T-cell leukemia (irregular cytoplasmic villi)

Question 7

Other Animal Retroviruses cause what?

Answer 7

Immunideficiency

Cancers: can cause much more varied forms than in human retroviruses
o Sarcomas: connective tissue
o Lymphomas and leukemia: hematopoietic
o Erythroleukemias: hematopoietic
o Reticuloendothelial tumors: macrophages
o Mammary carcinoma

Question 8

Retroviruses

Genome:

Answer 8

Genome: 2 identical strands of +ssRNA

Flow of Genetic Information: RNA –> DNA –> RNA

Question 9

Reverse Transcriptase

Type of polymerase:
What leads to mutations in retroviruses?

Answer 9

Reverse Transcriptase: RNA/DNA-dependent DNA polymerase that allows for reverse transcription of RNA to DNA; error prone leading to mutations in retroviruses (hard to treat)

Question 10

Genera

Alpharetrovirus:
Betaretrovirus:

Answer 10

Alpharetrovirus: avian-leukosis virus related (ie. RSV)

Betaretrovirus: B-type (ie. mouse mammary tumor virus)

Question 11

Genera

Deltaretrovirus:
Gammaretrovirus:

Answer 11

Deltaretrovirus: HTLV-I and II

Gammaretrovirus: C-type (more electron dense with centrally located capsid; feline leukemia virus)

Question 12

Genera

Epsilonretrovirus:
Lentivirus:
Spumavirus:

Answer 12

Epsilonretrovirus: walleye dermal sarcoma virus (seasonal)

Lentivirus: slowly progressive chronic infections involving neurologic impairment (HIV)

Spumavirus: chimpanzee foamy virus (foamy degeneration of infected cells by causes no known disease)

Question 13

Virion Morphology

Shape and Size:
What do envelope membranes contain?
Type of capsid?

Answer 13

General Structure:
Spherical and 80-100nm in diameter

Envelope membranes contain viral glycoprotein and cell lipids

Icosahedral capsid

Question 14

Important Viral Proteins

SU:

Answer 14

SU: surface (gp120)

Question 15

Important Viral Proteins

TM:

Answer 15

TM: transmembrane (gp41)

Question 16

Important Viral Proteins

MA:

Answer 16

MA: matrix (p17)

Question 17

Important Viral Proteins

CA:

Answer 17

CA: capsid (most abundant protein of retroviruses; p24)

Question 18

Important Viral Proteins
NC:
-Attached to:
-Responsible for:

Answer 18

NC: nucleocapsid (attached to RNA; responsible for packaging RNA; p7)

Question 19

Important Viral Proteins
RT:
- Attached to:
- Uses:

Answer 19

RT: reverse transcriptase (attached to RNA; uses tRNA primer that is also attached; p66)

Question 20

What is the most abundant protein of retroviruses?

Answer 20

CA: capsid

Question 21

Important Viral Proteins
PR:
- Cleaves:

Answer 21

PR: protease (cleaves polypeptide precursors)

Question 22

Important Viral Proteins
IN:
- Functions in:

Answer 22

IN: integrase (functions in replication; p32)

Question 23

Simple Genome: (3)

Answer 23

Gag
Pol
Env

Question 24

Gag:

Answer 24

Gag: CA, NC, MA

Question 25

Pol:

Answer 25

Pol: PR, RT, IN

Question 26

Env:

Answer 26

Env: SU, TM

Question 27

Complex Genome Examples include: Contain:

Answer 27

Complex Genome: examples include HIV and HTLV (those that infect humans) Contain gag/pol/env coding for the same proteins as simple genome PLUS other smaller accessory proteins

Question 28

RETROVIRUS REPLICATION General Infectious Process What does HIV bind? What happens to envelope proteins after fusion?

Answer 28

Virus binds host: in the case of HIV, receptor on host cell is CD4 Fusion: and entry of virus into host cell (envelope proteins left behind)

Question 29

RETROVIRUS REPLICATION General Infectious Process RT action: Where is the dsDNA translocated to?

Answer 29

RT Action: viral RNA --> ssDNA --> dsDNA Translocation of dsDNA into nucleus of infected cell

Question 30

RETROVIRUS REPLICATION General Infectious Process How is dsDNA integrated into the host DNA? What does it form? How is the provirus transcribed?

Answer 30

Integration: of dsDNA (viral) into host DNA using integrase enzyme (forms a provirus) Transcription of provirus: now uses host cell proteins (RNA polymerase II from host converts viral dsDNA back to ssRNA)

Question 31

RETROVIRUS REPLICATION General Infectious Process What happens after viral proteins are transcribed?

Answer 31

Translation of viral proteins: packaged and sent to the cell surface Budding: and release of mature retrovirus

Question 32

Transcription of Viral RNA Unspliced RNA What is unspliced viral RNA similar to? What is packaged into viral particles? Proteins:

Answer 32

Unspliced RNA: structurally similar to cellular mRNA (5’ cap and 3’ poly A tail) Viral genome (this is what is packaged into viral particles) mRNA for structure proteins (Gag and Gag-Pol polyproteins)

Question 33

Transcription of Viral RNA Single-splice RNA Occurs where? Proteins:

Answer 33

Single-splice RNA: occurs in simple genomes | o Env polyproteins

Question 34

Transcription of Viral RNA Multiple-splice mRNA Occurs where? Regulatory proteins: (3)

Answer 34

Multiple-splice mRNA: occurs in complex genomes Regulatory proteins (HIV Tat and Rev)

Question 35

Transcription of Viral RNA Multiple-splice mRNA Accessory proteins: (3)

Answer 35

Multiple-splice mRNA: occurs in complex genomes Accessory proteins (HIV Vif, Vpr, Nef)

Question 36

Synthesis of Viral Proteins Gag and Pol Proteins How are they synthesized? What does PR do?

Answer 36

Synthesized as large precursor polyproteins Gag and Gag-Pol polyproteins cleaved into mature proteins by viral protease (PR)

Question 37

``` Synthesis of Viral Proteins Envelope Proteins (SU and TM) ``` Produced by: What cleaves to SU and TM?

Answer 37

Produced by cleavage of a polyprotein Cleaved to SU and TM by cellular protease

Question 38

MECHANISMS OF RETROVIRAL TRANSFORMATION Definition of cellular transformation:

Answer 38

Definition of cellular transformation: a stable, heritable change in the growth control of cells

Question 39

MECHANISMS OF RETROVIRAL TRANSFORMATION Two Major Mechanisms:

Answer 39

Transduction of an Oncogene Insertional Mutagenesis

Question 40

MECHANISMS OF RETROVIRAL TRANSFORMATION Transduction of an Oncogene:

Answer 40

Transduction of an Oncogene: acutely-transforming retroviruses can carry an oncogene of cellular origin

Question 41

MECHANISMS OF RETROVIRAL TRANSFORMATION Insertional Mutagenesis:

Answer 41

Insertional Mutagenesis: provirus integration adjacent to a cellular proto-oncogene; results in high levels of a normal protein

Question 42

MECHANISMS OF RETROVIRAL TRANSFORMATION Transduction of an Oncogene Mechanism:

Answer 42

Mechanism: viral particle infects cell --> oncogene is expressed --> transformation occurs - Many viruses have acquired oncogenes from various different types of normal cellular genes

Question 43

MECHANISMS OF RETROVIRAL TRANSFORMATION Transduction of an Oncogene Oncogene:

Answer 43

Oncogene: a gene that causes cancer; arises from a proto-oncogene due to some form of genetic damage or abnormal expression