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HIV Pathogenesis Flashcards

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1
Q

What family does HIV belong to?

A

Retroviridae

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2
Q

What does retroviridae family do to replicate?

A

RNA viruses which use RNA-dependent DNA polymerase (reverse transcriptase) to make a cDNA replication intermediate

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3
Q

What was HIV originally named?

A

HTLV-3

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4
Q

When was ‘HIV’ first reported?

A

1981

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5
Q

Does HIV-1 or 2 have more virulence and infectivity?

A

HIV-1
Is the most prevalent, highest virulence and high infectivity

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6
Q

Where does HIV-1 come from?

A

Common chipanzee

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7
Q

Where does HIV-2 come from?

A

Sooty mangabey

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8
Q

What are the 4 groups of HIV-1?

A

M, N, O, P

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9
Q

What is the most common HIV group?

A

Group M

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10
Q

Where is HIV-2 largely restricted to?

A

West Africa

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11
Q

What is the predominant subtype of HIV-1 group M?

A

Subtype C (makes up 52% of HIV cases)

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12
Q

What is the significance of HIV subtypes?

A

Impacts viral load testing, vaccine design and drug resistance as tests have to test all subtypes otherwise it wont work

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13
Q

What can you do with SIV sampling?

A

Sample a gorilla SIVs in different sites across Congo etc. and map onto phylogenetic trees, starts to map where these different HIV variants might have come from in the SIV ancestors based on their phylogenetic relationships

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14
Q

What does HIV rapidly evolve to form

A

A quasispecies due to its error rate of RT

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15
Q

How do you estimate the rate of HIV-1 evolution?

A

Dol = distance ‘outgroup’ vs ‘late’
Doe = distance ‘outgroup’ vs ‘early’
d = Dol-doe
t = time difference

Rate = d/t
(See diagram on lecture to make sense)

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16
Q

What is there at each end of the genome?

A

Long terminal repeats

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17
Q

What is the main structural protein?

A

Gag

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18
Q

What is the gag polyprotein made up of?

A

Capsid, matrix and nucleoprotein

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19
Q

What function does pol have?

A

Has enzymes virus needs in order to infect a cell e.g. protease, reverse transcriptase etc.

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20
Q

What are the two subunits of env?

A

Gp120, gp41

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21
Q

What are the two regulatory genes?

A

Tat and rev

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22
Q

What are the accessory genes?

A

Nef
Vif
Vpr
Vpu

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23
Q

What do accessory genes do?

Study These Flashcards
A

Control teh host in some way e.g. inhibiting resitrction factors

24
Q

What does vpr do?

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A

Keeps cell in G2 cell cycle phase

25
What does vpu do?
An accessory protein invovled in antagonism of resitrction factors most famously for tetherin antagonism
26
What does APOBEC3 protein do and what does HIV do to it?
It induces random mutations VIF targets ABOBEC3 and takes it away so it can no longer be incorporated into budding virion
27
What is the relationship between HIV resitrction and tetherin?
Tetherin tethers budding virions to cell surface of productively infected T cells, vpu pritein comes along and snips it off cell surface and takes it away from the cell
28
What is the receptor for HIV viruses?
CD4
29
What do most basic lentiviruses not need that HIV does?
Accessory proteins
30
What are the two co receptors for HIV?
CCR5 and CXCR4
31
Where is CXCR4 mainly found?
On T cells, happens later in infection
32
Where is CCR5 mainly found?
In dendritic cells and other mucosal cells where the virus initially infects
33
What happen with HIV viral entry?
Virus binds to receptor and undergoes conformational changes, interacts with co-receptor, this change exposes fusion peptide inside the strutcure and comes thorugh and embeds itself into the membrane
34
Which steps are reversible vs irreversible?
First two entry steps, binding to CD4 and binding to co receptor are reversible But once fusion peptide is released then it can no longer be reversed
35
What is important about the HIV genome?
LTRs are identical to each other
36
What is the reverse transcription process?
TRNA acts as a primer for synthesis RT sits on end of the tRNA and synthesise DNA from RNA genome of the virus until it reaches 5’ end of the genome At this point RNAse and chews up RNA that is in complex with the DNA End up with a sticky end Have piece of ssDNA hanging off end of genome with tNRA holding it in place As 3’ end and 5’ end are identical, 3’ end of this sticky end can bind to 3’ end of RNA genome then DNa polymerase can carry on running along, copy the DNA and keep making DNA along the circle
37
What are the effects of variability?
Immune escape by changing/masking antigenic determinants Resistance to anti-retro viral drugs Altered cytopathogencitiy
38
What is the integration process?
Once dsDNA arrives at nucleus, can be extrachromosomal circular or linear or can integrate into host DNA During integration , two bases are removed from the ends by integrase, this creates a sticky end The integrase will also Knick two bases and create a stick end inside the host genome, get ligation reaction Ligases the genome into the host DNA repair processes repair broken ends and it will be fully integrated into the cell
39
Where is there a ribosomal frameshift between gag and pol?
Between gag and pol
40
What are the transmission methods of HIV?
Transcutaneous e.g. needle-stick injury Sexual Vertical (mother-infant)
41
What are disease stages classified as?
A, B, C With 1, 2, 3 subtypes Based on CD4 counts, can classify what clinical progression they are in through it
42
What is category A?
Asymptomatic or acute
43
What is category B?
Symptomatic
44
What is category C?
AIDS-indicator conditions
45
What are subtypes 1, 2, 3 based on?
Number of CD4 counts
46
What happens in acute phase infection with antibodies and antigen levels?
HIV-1 antibody negative HIV-1 RNA/ antigen positive
47
What happens in seroconversion stage of HIV-1 acute phase?
HIV-1 anitbody positive Decreased viraemia (RNA decrease, antigen decrease)
48
What receptor is primarily used in asymptomatic phase?
CCR5
49
What receptor is primarily used in symptomatic phase?
CXCR4 receptor
50
What is the CD4 count usually above for asymptomatic phase?
CD4 >200
51
What is the defect that causes people to be resistant to infection?
Delta32 - CCR5
52
What is the difference between homozygous delta 32-CCR5 and heterozygous?
Homozygote - very resistant to HIV-1 infection Heterozygous - delayed onset of AIDS, some resistance to infection
53
What stem cell transplant can cure HIV?
Stem cell transplant from delta 32 knockout human
54
Why were some sex-workers HIV-1 negative following exposure?
Had HLA subtypes that make them particularly resistant to HIV infection Means people never seroconvert to HIV
55
Why are some HLAs protective and others not?
Virus escape Some mutaitons neutral Some induce fitness cost

Viral Pathogenesis And Infection (16 decks)

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