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Microimm 2500 > (V) 26: HIV Pathogenesis > Flashcards

(V) 26: HIV Pathogenesis Flashcards

1
Q

First document cases of AIDS

A

in big metropolitan areas: LA + NY

Young men were having serious lung infections
- pneumocystis pneumonia caused by a fungus (should have a strong enough immune system to fight it)
- found out they had HIV + AIDS = no immune sustem

Some men had Kaposi Sarcoma (rare in younger pop.)
- lesions around neck, back + mouth
- “new” form of cancer

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2
Q

AIDS

A

Acquired Immune Deficiency Syndrome

Lots of misinformation about the virus

BUT transmission can also occur at BIRTH or HETEROSEXUALLY or with NEEDLES

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3
Q

AIDS Numbers

A

Ppl die from AIDS every couple of seconds

ppl living with AIDS is larger than Canadian population

AIDS has ravaged populations more effectively than war

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4
Q

Global HIV/AIDS

A

most infections are in SUB-SAHARAN AFRICA

COVID vaccine is less effective in certain parts of the world partly b/c of HIV rates around the world (ex. less effective in South Africa - immune system is not strong)

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5
Q

cART

A

combined Antiretroviral therapy

cocktail - many drugs attack virus @ various stages of replication = regulates replication

  • suppresses virus from replicating
  • need to take DAILY to be effective
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6
Q

When did HIV/AIDS therapy increase?

A

When the annual meeting of the International AIDS Society was held in South Africa in 2000

  • after this, more ppl in subsaharan Africa got antiretroviral therapy
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7
Q

Income and HIV

A

Lower income = higher rate of infection

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8
Q

Retroviridae

A

Family of virus
Subfamily: Lentiviruses
(+)ssRNA virus

2 viruses from subfamily infect humans: HIV-1 + HIV-2
- have an ENVELOPE

  • Rev. Transcriptase makes DNA from RNA
  • ssDNA CANNOT be transcribed
  • cellular DNA Poly makes dsDNA (can be integrated into genome forever)
  • dsDNA is transcribed to mRNA
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9
Q

Retrovirus Life Cycle

A

Early
1. Binding
2. Fusion and entry (envelope fuses w/ host cell memb. + loses shell)
3. Uncoating; Reverse transcription
4. Nuclear entry (dsDNA enters into nucleus of cell)
5. integration (enzymes snip parts of viral DNA + integrates itself into host chromosomal DNA)

Late
6. Transcription
7. Translation
8. Assembly
9. Budding
10. Maturation

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10
Q

HIV proteins and envelope

A

Surface protein (SU) = gp 120
Transmembrane protein (TM) = gp41
Capsid protein (CA) = p24

viral envelope glycoproteins embed themselves within envelope
- glycoproteins interact WITH HOST

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11
Q

SU

A

Surface protein = gp120 (glycoprotein and 120 is molecular weight)

VIRAL RECEPTOR

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12
Q

TM

A

Transmembrane protein = gp41

FUSION PROTEIN

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13
Q

CA

A

Capsid protein = p24

CAPSID PROTEIN

capsid box that protects genome

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14
Q

How do retroviruses integrate in host genome?

A

Due to production of dsDNA in retroviruses

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15
Q

Reverse Transcriptase

A

Polymerase lacks 3’-5’ exonuclease activity (proofreading)
- results in 1-10 NUCLEOTIDE ERRORS per synthesis

these errors cause heterogeneity in retroviruses = a collection of variants or QUASISPECIES (every case is unique = why HIV is so hard to treat)

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16
Q

Retrovirus genome parts

A

Gag: protective structural proteins
Pol: Polymerase; make protease (pr) proteins; enzyme
Env: envelope; genome region makes proteins embedded in envelope

17
Q

Gag

A

Protective structural proteins

Made up of:
- MA: matrix
- NC: nucleocapsid
- CA: capsid

18
Q

Pol

A

Polymerase
- makes protease proteins

Made up of:
- PR: protease (molecular scissors)
- RT: Reverse Transcriptase
- IN: integrase (snips genome to allow integration)

19
Q

Env

A

Envelope

Made up of:
- SU/gp21: surface protein
- TM/gp41: transmembrane protein

20
Q

Retrovirus genome

A

(+) ssRNA

7-10 kb long w/ nucleocapsid (NC)

21
Q

Integration of Retroviruses

A

PROVIRAL DNA (dsDNA) is integrated into cellular genome
- proviral DNA is transported from cytoplasm to nucleus

done by viral enzyme, INTEGRASE (in chromosomal AND viral DNA)
- integrase snips BOTH proviral + chromosomal DNA
- can get integration of viral DNA into human sequences forever

22
Q

Integrase

A

enzyme that snips both proviral and chromosomal DNA (and is expressed in both)
- can cause permanent integration of viral DNA into human sequences

  • removes two 3’-terminal nucleotides on each strand
  • viral DNA is inserted
  • free 3’ OH ends are ligated into a cleaved segment of host genome
23
Q

Origins of HIV/AIDS

A
  • cases in Central Africa
  • likely started in Zaire (now DRC)
  • almost all sex workers in Zaire and Rwanda were HIV+
24
Q

HIV Diversity

A

HIV-1 is the most prominent HIV virus (lots of variability)

  • based on sequence alignments
  • HIV-1 is split into 4 groups: M, N, O, P
  • HIV-1 Group M is major (90%) and is split into 9 subtypes A, B, C, D, F, G, H, J, K and CRFs

MOST of HIV-1 viruses are group M

Each group of HIV-1 (M,N,O,P) represents a transfer from an animal to a human

25
Q

Main group of HIV in North America

A

HIV-1, Group M, subtype B

26
Q

Subtypes of HIV-1

A

Subtypes A, B, C, D, F, G, H, J, K , CRFs

C: most prevalent in Africa
B: high in North America
D: quicker death
CRFs: usually in sex workers that have been infected many times

New subtype L in November 2019

27
Q

Main group of HIV worldwide

A

Group C is most prevalent in the world

28
Q

Highest subtype of HIV-1 in Africa

A

Group C

29
Q

CRFs

A

Circulating Recombinant Forms
- mixture of various subtypes

  • very pathogenic
  • common in sex workers who acquire different variants from multiple partners
30
Q

What subtype is most common in white MSM in South Africa?

A

Group B

MSM: men who have sex with men

31
Q

HIV-2

A

less common

  • not as transmissible
  • not as deadly
  • does not progress to AIDS as quickly
32
Q

HIV-1 source

A

HIV-1 is likely fro SIV cpz (simean immunodeficiency virus - chimps)

sequencing showed it was similar to the lentivirus (SIV)

33
Q

SIV and HIV-1

A
  • virus measured in fecal samples of chimp populations
  • chimps don’t swim = can isolate SIV populations by water
  • two types of chimbs both express SIV: Pan troglodytes schweinfurthii, Pan troglodytes troglodytes

SIV from PAN TROGLODYTES TROGLODYTES matches HIV-1 (origin)

34
Q

Old Word Monkeys

A

Old Word Monkeys have virus but are not sick (non-pathogenic)

chimps are vegetarians but must have eaten infected Old Word Monkeys to get SIV which was then transmitted to humans

Not pathogenic to Old Word Monkeys but pathogenic to chimps

35
Q

HIV-1 Tranmission

A

4 chimp cross-over events to humans
- epicentre was Kinshasa (Zaire)

BUSHMEAT HUNTING - for fur and meat
- exchange of blood btwn humans + chimps – biting, machetes, etc.
- there was likely an ACCELERATOR

First transmission to human is thought to be group M

36
Q

Accelerator for HIV-1 Transmission

A

Could be:

European colonization: urban centres, sex workers
- men transported themselves to Africa and created sex worker industry = contributed to spread of HIV

Intro to health cate to African population

37
Q

Ways HIV-1 is transmitted

A

Sexually-transmitted; IV drug use; blood transfusions; at birth

1/1000 chance to transmit HIV during coital act

HIV-1 is pretty whimpy - 10% bleach, heat, air drying or pH variance will inactivate it

Microimm 2500 (29 decks)

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