Yoshimura: Retroviruses Flashcards

1
Q

Human Retroviruses that cause Immunodeficiency:

A

HIV-I and HIV-II

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2
Q

Human Retroviruses that cause cancer:

A

HTLV-I and HTLV-II

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3
Q

HTLV-I causes:

Why does it only affect adults?

A

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

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4
Q

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

A

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

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5
Q

How common are HTLV-caused diseases?

HTLV is endemic where?

A

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

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6
Q

HTLV-II causes:

A

Hairy T-cell leukemia (irregular cytoplasmic villi)

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7
Q

Other Animal Retroviruses cause what?

A

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

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8
Q

Retroviruses

Genome:

A

Genome: 2 identical strands of +ssRNA

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

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9
Q

Reverse Transcriptase

Type of polymerase:
What leads to mutations in retroviruses?

A

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)

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10
Q

Genera

Alpharetrovirus:
Betaretrovirus:

A

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

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

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11
Q

Genera

Deltaretrovirus:
Gammaretrovirus:

A

Deltaretrovirus: HTLV-I and II

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

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12
Q

Genera

Epsilonretrovirus:
Lentivirus:
Spumavirus:

A

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)

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13
Q

Virion Morphology

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

A

General Structure:
Spherical and 80-100nm in diameter

Envelope membranes contain viral glycoprotein and cell lipids

Icosahedral capsid

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14
Q

Important Viral Proteins

SU:

A

SU: surface (gp120)

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15
Q

Important Viral Proteins

TM:

A

TM: transmembrane (gp41)

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16
Q

Important Viral Proteins

MA:

A

MA: matrix (p17)

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17
Q

Important Viral Proteins

CA:

A

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

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18
Q

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

A

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

19
Q

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

A

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

20
Q

What is the most abundant protein of retroviruses?

A

CA: capsid

21
Q

Important Viral Proteins
PR:
- Cleaves:

A

PR: protease (cleaves polypeptide precursors)

22
Q

Important Viral Proteins
IN:
- Functions in:

A

IN: integrase (functions in replication; p32)

23
Q

Simple Genome: (3)

A

Gag
Pol
Env

24
Q

Gag:

A

Gag: CA, NC, MA

25
Q

Pol:

A

Pol: PR, RT, IN

26
Q

Env:

A

Env: SU, TM

27
Q

Complex Genome

Examples include:
Contain:

A

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

28
Q

RETROVIRUS REPLICATION
General Infectious Process

What does HIV bind?
What happens to envelope proteins after fusion?

A

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)

29
Q

RETROVIRUS REPLICATION
General Infectious Process

RT action:
Where is the dsDNA translocated to?

A

RT Action: viral RNA –> ssDNA –> dsDNA

Translocation of dsDNA into nucleus of infected cell

30
Q

RETROVIRUS REPLICATION
General Infectious Process

How is dsDNA integrated into the host DNA? What does it form?

How is the provirus transcribed?

A

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)

31
Q

RETROVIRUS REPLICATION
General Infectious Process

What happens after viral proteins are transcribed?

A

Translation of viral proteins: packaged and sent to the cell surface

Budding: and release of mature retrovirus

32
Q

Transcription of Viral RNA
Unspliced RNA

What is unspliced viral RNA similar to?
What is packaged into viral particles?
Proteins:

A

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)

33
Q

Transcription of Viral RNA
Single-splice RNA

Occurs where?
Proteins:

A

Single-splice RNA: occurs in simple genomes

o Env polyproteins

34
Q

Transcription of Viral RNA
Multiple-splice mRNA

Occurs where?
Regulatory proteins: (3)

A

Multiple-splice mRNA: occurs in complex genomes

Regulatory proteins (HIV Tat and Rev)

35
Q

Transcription of Viral RNA
Multiple-splice mRNA

Accessory proteins: (3)

A

Multiple-splice mRNA: occurs in complex genomes

Accessory proteins (HIV Vif, Vpr, Nef)

36
Q

Synthesis of Viral Proteins
Gag and Pol Proteins

How are they synthesized?
What does PR do?

A

Synthesized as large precursor polyproteins

Gag and Gag-Pol polyproteins cleaved into mature proteins by viral protease (PR)

37
Q
Synthesis of Viral Proteins
Envelope Proteins (SU and TM)

Produced by:
What cleaves to SU and TM?

A

Produced by cleavage of a polyprotein

Cleaved to SU and TM by cellular protease

38
Q

MECHANISMS OF RETROVIRAL TRANSFORMATION

Definition of cellular transformation:

A

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

39
Q

MECHANISMS OF RETROVIRAL TRANSFORMATION

Two Major Mechanisms:

A

Transduction of an Oncogene

Insertional Mutagenesis

40
Q

MECHANISMS OF RETROVIRAL TRANSFORMATION

Transduction of an Oncogene:

A

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

41
Q

MECHANISMS OF RETROVIRAL TRANSFORMATION

Insertional Mutagenesis:

A

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

42
Q

MECHANISMS OF RETROVIRAL TRANSFORMATION

Transduction of an Oncogene
Mechanism:

A

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

43
Q

MECHANISMS OF RETROVIRAL TRANSFORMATION

Transduction of an Oncogene
Oncogene:

A

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