Human immunodeficiency virus L14

Question 1

what does HIV lead to

Answer 1

AIDS
- acquired immunodeficiency syndrome
- Unusual infections and tumours
e.g. pneumocystis
Kaposi’s sarcoma (HSV-8)

Question 2

how is HIV transmitted

Answer 2

1. sexually
2. mechanically
   - needles, surgery, blood transfusions
3. verticle
   - prenatal via placenta or birth
   - post-natal via breast milk

Question 3

how have cases have HIV lowered

Answer 3

education
- protective sex
- needle hygiene
drugs
-triple therapy

Question 4

what are the two types of HIV

Answer 4

HIV1 and HIV2
- HIV1 much more infectious

Question 5

where did HIV originate from

Answer 5

Simian immunodeficiency virus (SIV) from monkeys
- Chimpanzee SIV: homology with HIV-1
- Sooty Mangabey SIV: homology with HIV-2
- SIV much milder disease
Zoonosis example- probs when local people where hunting or butchering animals- blood contamination, eventually evolved to HIV- so can spread through human pop

Question 6

what are the common features of retrovirus

Answer 6

Retrovirus family – common features:
Reverse transcriptase
Wasting
Immunodeficiency
Dementia

Question 7

describe the structure of HIV

Answer 7

1. has two, single stranded coding RNA
2. has integrase and reverse transcriptase enzymes
   - surrounded by P24 capsid protein
3. P17 matrix protein surrounds capsid in isochehdral shape
4. has a lipid bilayer envelope
5. GP120 and GP41 surface glycoproteins

Question 8

which receptor does gp120 bind to

Answer 8

CCR5 receptor (on macrophage and some CD4+ T cells; early infection)
or CXCR4 (on most CD4+ T cells; late infection)

Question 9

what is the functions of Reverse transcriptase

Answer 9

1. it is an RNA dependant DNA polymerase
   - turn RNA into neg DNA strand
2. acts as RNAse
   - hydrolyses RNA leaving cDNA
3. acts as DNA dependant DNA polymerase
   - uses cDNA to synthesise second strand of DNA

Question 10

what does intergrase recognise and what does it do

Answer 10

recognises unique sequences called long terminal repeats at 5’ and 3’
allows the DNA to be inserted into host chromosome
remains latent until cells are activated

Question 11

What happens once host cell is activated

Answer 11

translation of viral polyproteins start
1. gag - encodes P17 and P24 capsid proteins
2. Pol - encodes intergrase and RT
3. ENV - encodes GP41 and GP120

Question 12

how does HIV lead to AIDS

Answer 12

CD4T cells encounters complementary antigen it becomes activates leading to further activation of other cells eg CD8 cytotoxic T cells that destroyed virally infected cells
Also activate b cells that produce antibodies
CD4T cells produce signalling molecule that activates transcription of viral genome and important immune proteins
- HIV stops this from happening weakening the immune system

Question 13

describe the effect HIV has on CD4T cells

Answer 13

at primary infection, HIV rises and CD4T cells decrease
then CD4T cells start to increase and HIV decreases slightly and enters clinical latency
over many years, CD4T cells decrease and HIV RNA copies increases leading to death

Question 14

give some Opportunistic infections associated with HIV-1 infection

Answer 14

Pneumocystis sp.
TB (Mycobacterium tuberculosis)
Malaria (Plasmodium falciparum)
Candida sp. (thrush)
Toxoplasma sp.

Human papilloma Virus (HPV)
- cause genital, skin and oral cancers

Question 15

what viruses can activate latent infections

Answer 15

Herpes viruses:
Varicella zoster virus - Shingles
Epstein Barr virus - B-cell lymphomas
Cytomegalovirus- lymphomas
HSV-8 - Kaposi’s sarcoma

Question 16

how can we prevent HIV 1

Answer 16

1. eduction
2. vaccine
   - however, as HIV is RNA which has no proofreading abilities, mutations are not corrected so HIV mutates a lot so vaccines may not be effective for very long
   - Mucosal infection – subcutaneous vaccines
   poor protection of mucosal surfaces
   - No good animal model

Question 17

give examples of HIV therapies

Answer 17

1. Triple therapy – Highly active anti-retroviral therapy (HAART)
2. Nucleoside analogues e.g. abacavir – competitive inhibitor of RT
3. Peptide analogues – e.g. saquinavir – competitive inhibitor of HIV protease
4. Anti-CCR5 therapy?? - individuals with mutation in CCR5 gene are highly resistant to HIV. Blocking CCR5 or bone marrow transplant from CCR5 defective individuals are possible therapeutic interventions.