Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Microbiology > Exam3Lec2Retroviruses/OncogenicViruses > Flashcards

Exam3Lec2Retroviruses/OncogenicViruses Flashcards

1
Q

What genus of the retroviridae family affects human? What are its features and list its examples

list the two related to this lecture

A
  • Deltaretrovirus, complex onco, human T cell leukemia virus
  • Lentivirus, complex, humman immunodeficiency virus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What genus of the retroviridae family affects animals? What are its features and list its examples

A

alpha,betam and gamma retrovirus. features for all three are simple and oncogenic

examples: alpha-ALV (avian leukemia virus)
beta- MMTV (mouse mammry tumor virus)
gamma -MLV (murine leukemia virus)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Explain the retrovirus virion

A

It has a genome with a capsid in lipid bilayer
TM: transmembrane holds the globualar part
When it comes into the cell, it has to break in and it does rev. transcriptase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the nuclear phase of replication of retroviruses?

A

Integrate into host genome (provirus)
All contain reverse transcriptase

turns RNA genome into cDNA provirus, this integraates into host genome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the two classes of retroviruses?

A
  1. Simple retroviruses: encode Gag, Pol, and Env. Requires cell division for integration
  2. Complex retroviruses: encode Gag, Pol, Env + several small regulatory proteins. (more in their genome) DO NOT require cell division for integration. (Ex: HTLV-1 & HIV)

nucelor import of retrovirus proviral DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Explain the retrovirus life cycle (replication)

A
  1. Receptor mediated membrane fusion or penetration then partial uncoating
  2. Rev transcriptase and RNAse-H
  3. nuclear translocation and Integration of cDNA into genome of the host (cDNA moves into nucleus)
    host cell machinery takes over
  4. Transcription: RNA is exposed and spliced to make diff proteins
  5. Translation of viral protein: 2 copies of RNA. One does capsid assembly other goes through golgi They both then move to membrane for budding
  6. Protease mediated virion maturation after budding (release by budding)

after they uncoat, they use rev transcriptase to make dna copy of genome, goes into nucleus and integrates into provirus genome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are 4 unique features of retroviral replication?

A
  1. Diplpid +RNA genome
  2. Genome is not directly translated
  3. Genome is reverse transcribed into cDNA provirus
  4. Integration of provirus into infected cell chrmosome

1st rev. transcription to make cDNA proteins and then it integrates into cell DNA. Then provirus is transcribed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Explain the structure of Proviral DNA?

A
  • LTR: long terminal repeat (provides promoter activity)
  • GAG: structural proteins of virion
  • POL: Enzymatic activities
  • ENV: virion envelope glycoprotiens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is LTR?

A

Long terminal repeat. It is the “gps” for DNA provirus to make sure it integrates into the right area in the host genome

it does this by copying both sides of RNA genome and thats how cDNA knows where to go.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is GAG?

A

structural proteins of the virion
MA: matrix
CA: capsid
NC: nucleocapsid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is POL?

A

Enzymatic activities
RT: reverse transcriptase
RN: RNaseH
PR: Protease
IN: Integrase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is ENV?

A

virion envelope glycoproteins
SU: surface
TM: transmembrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the two types of oncogenic retroviruses?

A

Transducing and Non-transducing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are transducing oncogenic retrovirsues?

A

HIGHLY carcinogenic
Cause cancer because their genomes contain altered cellular genes called v-oncogenes which are transduced.

cause malignancies in 100% of infected animals in a matter of days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are non-transducing oncogenic retroviruses?

A

LESS carcinogenic
DO NOT encode v-oncogenes
Activate transcription of proto-oncogenes by integration of the provirus

do not 100% cause cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What do Viral Oncogenes alter?

A
  1. Growth factors
  2. Growth factor receptors
  3. Intracellular tyrosine kinases
  4. Serine/Threonine kinases
  5. Signal transduction proteins
  6. Transcription factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is Human T-Lymphotropic Leukemia Virus?

A

retro family
(+)ss, enveloped, ico, 2 copies per virion (diploid)
replications in nucleus (reverse transcriptase integration)

Transmission: Sexual (bloodborne)
Tropism: T cells

these are in humans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What clinical diseases we see with HTLV-1

A

Clinical disease: Adult T cell Leukemia (ATL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

HTLV-1 causes what indirectly and how?

slide 11 on TA

A

Causes cancer indirectly
TAX proteins are mainly responsible for HVTL-1 to cause cancer in indirect way. Remember that complex retovirusus encode gag, pol, env, and many small regulatory proteins. TAX is on of those small regualtory proteins that causeses rapid replications of T cells which then causes genetic instablitlity, mutations occur.

20
Q

HTLV-1 oncogenesis

A
  1. Integration of single copy-provirus genome
  2. Effects HTLV-1 on host genes in cis and trans
  3. Genetic mutation, epigenetic modifications occur
  4. Frequent loss of tax expression
  5. ATL (adults t cell leukemia)

frequen loss of tax expression forces cells to prolif. alot then it causes DNA damage. SO more prolif of cell w/ genomes integrated incr genetic instability which leads to mutations, etc.

21
Q

Explain trans effects

A

impacts of provirus on infected and uninfected chromosomes.
* transactivation of host cellular pathways
* genetic instability by TAX protein
* susutained cell division in long-lived HTLV-1

22
Q

Explain HTLV-1 oncogenesis in terms of expression and suppresion of Tax.

A

T cell is infected with HTLV-1. Tax protein is expressed and expansion of infected CD4+ cells.
HTLV-1 makes reg proteins that supresses TAX (Rex, p30, HBZ). And our own immune response CTL (CD8+) suppresses TAX

Over time, expansion of infected cd4+ cells lead to alteration of genome and ATL

takes a long time for DNA damage to accumulate

23
Q

For endogenous retroviruses, retroviral elements make up about ___ to ___ percent of the human genome

A

7,8

we live with retrovirus

24
Q

True or False, Endogenous retroviruses vertical transmission (infection of germ line). Present in virtually all vertebrate genomes.

A

True

25
Q

Endogenous retrovirus are expressed during when?

A

during development or stress

Cell-Cell fusion in placenta (HERV-W, HERV-FRD -enveloped protein)

Without endo retroirus enveloped protein, there is no placenta.

26
Q

How does endogenous retroviruses prevent viral infection?

A
  • Enhance viral sensing pathways immune genes
  • regulate antiviral gene expression (turns on innate IS)
  • viral entry interference (blocks entry of other viruses)
  • restriction of virion assembly

also note that endo retroviruses induce cell proliferation

27
Q

What has major HIV clades?

A

chimpanzees

28
Q

What is the HIV-1 genetic organization

A
  • Unspliced-Gag-pol: Viral replication/assembly
  • Single-Env: virus attachement

these are different genes that code for small regulatory protein

look@table for the rest, teng put only 2 in red but laz highlighted everything.

29
Q

What is the HIV structure?

A

Env:
-gp120 surface
-gp41 transmembrane

gag:
-p17 matrix
-p24 capsid
-p7 nucleocapsid

pol
-p66/51 RT
-p32 Integrase
-p11 protease

this is a normal retrovirus
there is no ico capsid in the middle
Capsid is formed inside the virus and is encapsulated

30
Q

HIV-1 life cycle

A
  1. Free virus comes in
  2. Rev transcriptase
  3. DNA integration
  4. Transcription and assembly
  5. Budding and immature virus breaks free of the inf. cell
  6. Maturation: protein chain in the new viral particle are cut by the protease enzyme into individual proteins that combine to make a working virus.

like every other virus except one step
The mature capsid of the virus is made AFTER virus is released from the host( this occurs OUTSIDE the host cell, not in the cell)

31
Q

Explain HIV binding and entry

A

The gp120 has a specific domain that binds to the CD4 molecule present on susceptible cell causing fusion
Upon binding to CD4, the gp120 undergoes a conformational change that allos binding to chemokine coreceptors (CCR5 or CXCR4)

32
Q

What are the HIV Co-Receptors?

A

CXCR4 is the major co-receptor for T-cell-tropic strains: this is involved in progression to AIDS

CCR5 is the major co-receptor for macrophage-tropic strains: this is involed in transmission of infection

33
Q

Explain the Acute phase of HIV-1 infection

initial exposure to toxins

A
  • infection of CD4+ cells in lymph nodes (lymphadenopathy)
    * flu-like symptoms (fever, chills, headache)
  • slight decrease in CD4+ cell count (where virus is replicating)
  • increase in virus-specific CD8+ CTLs
  • early virus isolates show preference for macrophages
34
Q

Explain the asymptomatic phase of HIV-1 infection

A
  • Low viremia
  • minimal decrease in virus specifc CD8+ CTLs
  • Slow decline in CD4+ Tcells: result of CTL mediated killing of infected CD4+ T cells

low virus means that lower number of CD4 is killed

35
Q

Explain the symptomatic phase of HIV-1 infection: AIDS

A
  • CD4+ count below 200/ml
  • Total CD8+ numbers lowered (bc CD4 is being lowered and they work hand-in-hand)
  • Destruction of lymph nodes and lymphoid tissue
  • Homogenous virus isolates, T-cell tropic HIV
    -rapid replication of HIV-1 RNA, CD4+ cytopathic (killing of CD4 cells by virus itself)
  • Low sensitivity to neutralizing antibodies
36
Q

Explain the late symptomatic phase of HIV-1 infection: (<200 Cd4+ cells/ml)

A

Opportunistic infections
1. Protozial infection: pneumocystis jiroveci, toxoplasma gondii, cryptosporidia
2. Bacterial infections: mycobacterium avium, treponema pallidum
3. Fungal infections: candida albicans, cryptococcus neoformans
4. Viral infections: cytomegalovirus, HSV, EBV, Kaposi;s sarcoma (HHV-8), anogenital carcinoma (HPV)

Neurological sx: aspectic meningitism ataxia, AIDS dementia comples

IS is so depleted that y0ou are allowing opportunities for infections to infect the body. This is because you have aids, not necessarily being immunocompromised

37
Q

Adults and children living with HIV, newly infected with HIV, and deaths die to AIDs are highest in which region of the world?

A

Eastern and southern Africa

38
Q

Whar are the types of Anti-retroviral drugs?

A
  1. Entry inhibitors (blocks binding of CD4 to CR5)
  2. Integrase inhibitors
  3. Protease inhibitors
  4. Rev. transcriptase inhibitors

cocktail that target virus at diff parts of life cycle

39
Q

What are the Highly Active Anti-Retroviral Therapy (HAART) guidelines

A

current guidelines: 2 NRTI + INSTI
Alternates:
* 2 NRTIs + 3rd Class (INSTI, boosted-PI, or NNRTI)
1NRTI +INSTI (only 1 approved regimen)

NRTI: nuceloside RT inhibitos
INSTI: integrase inhibitor
NNRTI: Non nuceloside RT inhibitor
PI: protease inhibitor (requires pharmacokinetic booster)

40
Q

What are the two ways to prevent HIV?

A

PRE-Exposure Prophylaxis (PrEP)
POST-Exposure Prophylaxis (PEP)

41
Q

What is PRE-Exposure Prophylaxis (PrEP)

A

Prevention of infection and/or spread

PrEP consisits of an HIV cocktail: emtricitabine/tenofovir (NRTI combo)
Taken one daily and provides maximum protection after
-7 days for anal sex
-20 days for vaginal sex or injection drug use

you thibk you might be in a high risk situation

42
Q

What is POST-Exposure Prophylaxis (PEP)

A

Taken within 24-72 hours of possible exposure to HIV
PEP consists of HIV cocktail : raltegravir (INSTI) PLUS emtricitabine/tenofovir (NRTI combo)
Once prescribed, must be taken for 28 days

you were involved in a high risk situation

43
Q

Can a vaccine prevent HIV?

A

NO

44
Q

Explain the CCR5 delta 32 allele

A

32bp deletion in CCR5 gene=long term non-progressor
* otherwise immunocompetent but do have incr risk for flavivirus infection
* stem cell transplant with 32 bp deletion led to clearance in two cases
-HIV positive AML patient (Berlin)
-HIC-positive Hodgkins patient (London)

we have a pt where HIV cant affet them b/c they have a deletion with 32 bc in CCR5. This is not easily replicative

45
Q

Explain gene therapy vectors

A

MSCV (murine stem cell virus-not a human virus): retrovirus
* used for transduction of human hematopoietic cells b.c they integrate into genome
* chomeric antigen receptor (CAR) T cell therapy for CD19+

HIV: Lentiviurs (this is a human virus so making it safely is a problem)
* different generation of vectors resulting in increasd safety

introduce new proteins ino cells

46
Q

Explain Lentivirus (HIV) gene therapy vector

relisten

A

We modify its genome so it not infectious but where they can still integrate into host genome.

47
Q

Explain Ex Vivo delivery of Gene therapy

how do we use them?

A
  1. Cells are harvested from bone barrow and isolated and cultures
  2. Pop lentiviral vector into cell genome (transduce them with it)
  3. Lentiviral vector inserts into the DNA and we grow them in lab. (expressed in stem cells
  4. Put them back into patient

Microbiology (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions