HIV - virology & immnology

Question 1

6 steps of HIV virology

Answer 1

1. attachment
2. cell entry
3. interaction with host cells
4. replication
5. assembly
6. release

Question 2

describe attachment

Answer 2

viral and cell receptors

Question 3

describe cell entry

Answer 3

only central viral ‘core’ carrying the nucleic acid and some associated proteins enter host cell

Question 4

describe interactions with host cells

Answer 4

use cell materials (enzymes, amino acids, nucleotides) for their replication; subvert host cell defence mechanisms

Question 5

describe replication

Answer 5

may localise in nucleus or in cytoplasm or in both

production of progeny viral nucleic acid and proteins

Question 6

describe assembly

Answer 6

occurs in nucleus, in cytoplasm or at cell membrane

Question 7

describe release

Answer 7

by bursting open of cell;
or by exocytosis from the cell over a period of time

Question 8

9 steps of replication of HIV

Answer 8

1. Attachment
2. Entry
3. Uncoating
4. Reverse transcription
5. Genome integration
6. Transcription of viral RNA
7. Splicing of mRNA and translation into proteins
8. Assembly of new virions
9. Budding

Question 9

what does HIV infect

Answer 9

HIV infects cells that express CD4 and the interaction between cd4 AND GP120 is conserved among all primate lentiviruses

Question 10

what does binding of gp120 to CD4 induce

Answer 10

a conformational change in gp120

Question 11

what does the co receptor binding site include

Answer 11

a conserved bridging sheet and also amino acids in the V3 loop

Question 12

describe immune response to HIV

Answer 12

Vigorous immune response but no demonstrable protective immunity with rare exceptions

Excessive immune activation which favours viral replication
Immunological dysfunction with involvement of all elements of host defence

Ongoing viral replication with progressive immunological impairment leading to clinical manifestations of immunodeficiency

Question 13

what is HIV-1

Answer 13

retrovirus that evolved from a simian immunodeficiency virus in chimpanzees

It replicates in CD4 positive cell
The virus copies its RNA into DNA and used the host cell for gene transcription

Question 14

what does HIV-1 result in

Answer 14

gradual damage to the immune system mainly through depletion of CD4 T-cells

Question 15

what kind of virus is HIV

Answer 15

A retrovirus - an RNA virus which uses reverse transcriptase to make a dna copy that becomes integrated into the DNA of the infected cell

Question 16

HIV genome structure

Answer 16

small rna virus - expresses just 10 genes

member of retrovirus family - uses reverse transcriptase to make DNA copy of itself

lentivirus - characterised by long incubation period

Question 17

how does HIV interact with CD4 receptor

Answer 17

HIV fuses to cd4 receptor and passes its contents into the CD4+ cell

Question 18

what are co receptors for HIV

Answer 18

CCR5 and CXCR4 chemokines receptors

Question 19

when is CCR5 used

Answer 19

used by HIV-1 in early infection byt may switch to use CXCR4 later in infection

once viral integration has occurred, infection persists for life in a reservoir of latently infected cells

Question 20

what are targets for antiretroviral therapy

Answer 20

integrate inhibitors
fusion/entry inhibitors
reverse transcriptase inhibitors
proteases inhibitors

Question 21

describe genetic resistance to hIV

Answer 21

1% of caucasians are homozygous for a 32bp deletion in the CCR5 gene - this is necessary for primary HIV1 ifnection

people wit only one copy of the mutant gene can be infected with HIV but show delayed disease progression

Question 22

why does HIV evolve rapidly

Answer 22

due to

• error prone replication (the enzyme reverse transcriptase makes at least 1 error in every replication cycle)
• rapid viral replication (generation time - 2.5 days)

-large population sizes

Question 23

what increases hIV-1 diversity

Answer 23

recombination between different classes/subtypes in the same person

Question 24

describe acute hIV-1 infection

Answer 24

detectedion of v high levels of virus in blood

symptoms of acute retro viral fever

Question 25

what are the symptoms of acute retro viral syndrome

Answer 25

glandular fever
fever
sore throat
oral ulcers
skin rash
neurological features

Question 26

what do immune responses during AHI (acute HIV0 determine

Answer 26

long term viral control

disease progression

Question 27

why is early invitation of acute hiv 1 ifnection beneficial

Answer 27

reduced risk of transmission

smaller reservoir

lower set point

delayed progression

Question 28

clinical features of untreated HIV-1

Answer 28

• vaginal/ oral candidiasis
• skin disease
• fatigue
• bacterial pneumonia
• herpes zoster
• oral hairy leuopkplakia
• thrush
• fever
• diarrhoea
• weight loss

Question 29

why does the immune response to hiv 1 not clear the virus

Answer 29

antibodies develop against most viral proteins, byt neutralising antibodies take months to develop and rarely neutralise the primary hiv strains that are transmitted from person to person

the response of CD4+ T helper cells is lost early on because HIV infects them first

there is a v vigorous response from cytotoxic CD8+ T cells which provides the major force controlling viral replication but fails when immune exhaustion sets in