Lecture 18: Retroviruses- HIV, AIDS, and more Flashcards

0
Q

How is HIV transmitted?

A

Due to the direct transfer of infected body fluids and infected cells.

  • Sexual contact
  • contaminated needles during drug abuse
  • medical tissue transfer (blood, etc)
  • fetal or neonatal transfer by infected mothers
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1
Q

What is HIV?

A

Human immunodeficiency Virus (HIV1-HIV 2) suppresses immune function, permitting normal flora and minor pathogens to cause multiple progressive debilitating disease that are ultimately fatal.

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2
Q

What are retroviruses ?

A

These viruses enter a cell as + sense ssRNA and are converted to DNA (the reverse of the host process)

Example : AIDS and T-cell leukemia

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3
Q

What are some characteristics of retroviruses?

A
  • Enveloped, 2 copies ssRNA+–> DNA
  • Integrate into host genome
  • long incubation periods
  • frequently change host range
  • cause human tumors and immunodeficiency
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4
Q

What was the first discovery that viruses could cause tumors?

A

1902 Dr. Rouse was studying chicken tumors, when he discovered that he could infect other chickens with the filtrate (allows tiny particles like viruses to pass) from the tumor.

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5
Q

Are retroviruses enveloped?

A
  • Retro viruses are enveloped viruses that contain two identical copies of positive-strand RNA.
  • Also contain reverse transcriptase that enzyme for transcribing RNA to DNA
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6
Q

What are the groups that retroviruses can be divided into?

A

3 Exogenous and 1 Endogenous

1) Oncoviruses
2) Lentiviruses
3) Spumaviruses
4) Endogenous viruses

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7
Q

What are Oncoviruses?

A
  • cause cancers in many different animals
  • They cause cancer by expressing analogs of cell growth-controlling genes
    example: oncogenes
  • Avian tumors
  • mammary tumors
  • Leukemias most species
  • HTLV I and II (Human leukemias)
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8
Q

What are Lentiviruses?

A
Cause slow-developing CNS and immunosuppressive diseases in a variety of animals 
Examples:
Fish Tumors
VISNA (sheep) lesions
HIV 1 and HIV 2 
SIV 1 (monkey AIDS) 
Horse, cow and cat AIDS
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9
Q

What are Spumaviruses ?

A

Where the first human retroviruses discovered but they are not associated with any known disease.

  • Cytopathic
  • Foamy
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10
Q

What are Endogenous viruses?

A
  • The ultimate parasite having permanently “integrated into our germ-line” DNA.
  • no longer fully functional viruses (degenerate)
  • transmitted vertically
  • not associated with any disease
  • 8% of our human genome (100,000 of them)
  • Integrated into genome
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11
Q

How many carriers in HIV

A

40 million carriers

-3 million AIDS cases

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12
Q

What are the 3 common ways to spread HIV ?

A

1) Blood
2) Sex
3) perinatal

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13
Q

What implications does the long asymptomatic period of the virus have?

A

The virus can long be spread before characteristics symptoms become identifiable and a person even knows they are infected.

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14
Q

Worldwide who is the primary means of transmission? In the US?

A

Heterosexual men and homosexual sex in the US, but heterosexual numbers are growing.

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15
Q

Who else is at serious risk for HIV?

A

Illicit IV drug users

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16
Q

Children born of HIV infected mothers stand a good chance of of becoming infected with the virus unless what?

A

The mother is undergoing antiviral (anti-HIV) therapy.

17
Q

What are some factors that cause a higher risk of HIV?

A
  1. increased sex partners
  2. Increased loss of epithelial barrier = higher risk of gonhorrhoeae, syphilis, herpes, etc.
  3. Increase virus and # / time = higher risk
    -Genital lesions
    -rectal tissue damage
    -
18
Q

When did HIV-1 first infect humans

A

100 years ago with HIV-2 following several decades later.

19
Q

True or False? As with most infectious diseases HIC and AIS primary impact the poor, w. 96% of newly infected coming from low/moderate income countries and minorities.

A

Yes, in the US 2/3 of the newly infected are now from the black and hispanic/latino communities.

20
Q

What are the 4 major gene segments present in all retroviruses have have a similar non-segmented genome structure?

A

1) GAG
2) PRO
3) POL
4) ENV
* With LTR at each end

21
Q

What does the gag genes code for

A

structural proteins such as the capsid

22
Q

What do the pro genes code for?

A

Viral protease

23
Q

What do the Pol genes code for?

A

the enzymes such as reverse transcriptase, which are responsible for replicating and integrating viral genome.

24
Q

What do the env genes code for?

A

For the 2 major spike proteins, GP 41, and GP 120

25
Q

What are the 6 main steps for HIV infection?

A

1) Attachment to a specific cell receptor ( HIV binds via GP120 to CD4 and a chemokine receptor CCR5 or CXCR4)
2) Entry in to the cell (GP 41 is required for the virus to fuse with the cell membrane)
3) Reverse transcription of viral RNA- HIV must carry reverse transcriptase with its since cells do not produce it
4) Integration of viral dsDNA in the host cell DNA
5) *Transcription and translation of viral DNA into mRNA and proteins. *
6) Assembly and maturation of new infectious HIV

Note: Steps 1,2,3,4 and 6 can be used for anti-HIV therapy and step 5 w/ unique regulators will some day too.

26
Q

For step 4 in HIV infection, The integration of viral dsDNA in to the host cell DNA. What does HIV carry to cleave the host DNA so the viral DNA can be inserted into it?

A

Integrase

27
Q

As the virus buds from the cell what completes the polypeptide cleavage and allowing it to eventually self-assemble into a mature infection ?

A

Protease

28
Q

What can block the fusion of the HIV virus?

A

Chemokines

29
Q

Do dsRNA viruses have a higher or lower mutation rate than ssRNA?

A
  • lower, because it does not have a second strand to check against to or have the ability to proof read.
  • Diploid nature 2 identical copies of the gene allows for more mutations to occur.
30
Q

What does the protease do?

A

It is renin-like enzyme that cuts unique site Tyr-Proline.

***When virus buds off protease is ACTIVE.

31
Q

What is the ligand for Gp 41?

What is the ligand for Gp120?

A

Gp 41= CCR5

Gp120= CD4

32
Q

Mostly Northern European have a small mutation in a ________ receptor that is used by HIV to bind/fuse with the host cell membranes. (Persons are double deletion (negative) of this gene)

A

CCR5

33
Q

What is the function of a mutated CCR5?

A

It appears to makes these individuals resistant to HIV infection, even after multiple exposures.

-Note: This is because the Gp 41 needs to bind to CCR5 in order to pull in HIV virus.

34
Q

What is the huge battle going on with the HIV-infected individuals for 8-12 yrs?

A

***Tc cells are killing huge number of HIV-infected Th cells every day! The body responds by making more Th cells but this cycle continues for years.

***Eventually Thymus can’t keep up producing these huge number of Th cells so as a RESULT Opportunist infections begin —>killing the individual.

35
Q

What drug extends the typical life span of an HIV infected individual from 3-5 years to 15-20 years ?

A

HAART therapy (Highly Active Antiretroviral Therapy)

  • Expensive
  • cocktail of antiviral, anti-parasitic, antibacterials…
36
Q

What are some other Anti-HIV Drugs in clinical use?

A

1) Reverse transcriptase inhibitors - nucleoside analog
2) Reverse transcriptase inhibitors-non nucleoside analog
3) Protease inhibitors
4) Entry (fusion) inhibitors
5) Integrase inhibitors

37
Q

What does a CD4 count below 50 indicate?

A

Serve disease and increased risk for opportunities infections like MAC and CMV

38
Q

What does a CD4 count between 50-200 indicate?

A

Increased risk for PCP (fungal infection) and other opportunistic infections and possibly preventative treatment for MAC and CMV (if below 100)

39
Q

What does the CD 4 count of 200-500 indicate?

A

Increased risk for shingles (zoster), thrush (Candida), skin infetions, bacterial sinus and lung infections, and TB.

Note: opportunists infections are rare

40
Q

When do oral diseases appear in AIDS patients?

A

First appear near the beginning of AIDS and continue throughout.

Note: Dentists are first to notice if AIDS has begun sometimes one doesn’t even know they are HIV +

41
Q

How does AIDS which results in immune suppression and dysfunction affect the mouth?

A

Results in opportunist infections and more severe typical oral diseases Like: (e.g necrotizing ulcerative gingivitis- NUG and necrotizing ulcerative periodontitis NUP) or Linear gingival erythema.

***This results in more aggressive oral Tx in AIDS patients is often called for.