2. HIV

Question 1

What behavioral and social factors contribute to heterosexually transmitted HIV epidemic?

Answer 1

• Little/no condom use
• Multiple partners
• Overlapping sexual partners
• Large sexual networks
• Age mixing; old men & young girls
• Women dependent on marriage/prostitution

Question 2

What biological factos contribute to heterosexually transmitted HIV epidemic?

Answer 2

• High STD rates (especially HSV-2)
• High viral loads
• Low rate of male circumcision

Question 3

What family does HIV belong to?

Answer 3

Retroviridae

Question 4

What is the HIV genome ?

Answer 4

Diploid linear 9.2kb + sense ssRNA

Question 5

Where is the virus assembled?

Answer 5

Cytoplasm - plasma membrane

Question 6

What is the origin of HIV-1

Answer 6

Evolved from SIVcpz (chimpanzee)

Question 7

What is the origin of HIV-2

Answer 7

SIVsmm

Question 8

What are the env genes?

Answer 8

1. SU-surface (gp120) = cell attachment

2. TM-transmembrane (gp41) = fusion domain

Question 9

What are the gag genes?

Answer 9

1. MA-Matrix (p17)
2. CA-Capdis (p24)
3. NC-Nucleocapsid (p7)

Question 10

What are the pol genes?

Answer 10

1. RT-Reverse transcriptase (p66/51)
2. IN-Interase (p31)
3. PR-Protease (p11)

Question 11

What is the function of the gag gene?

Answer 11

Structural proteins of the capsid, matrix, core and nucleocapsid

Question 12

What is the function of the pol gene?

Answer 12

Viral enzymes, expressed as Gag-Pol polyprotein before autoclavage

Question 13

What is the function of the env gene?

Answer 13

Envelope glycoproteins expressed from a spliced mRNA

Question 14

What is the life cycle of HIV?

Answer 14

• Binding
• Reverse transcription
• Provirus integrate into DNA
• Transcription of regulatory protein
• Re-uptake of regulatory protein back into nucleus (Rev)
• Full length progeny RNA
• Genomic RNA
• Budding
• Maturation

Question 15

Describe the entry process of HIV-1

Answer 15

• Attachment through non-specific cell receptors (CLR/Mannose R on Astrocytes)
• Structural changes in gp120 after binding to CD4
• Exposure of gp41 and binding to CCR5, CXCR4 promotes fusion and peptide insertion
• Strucutural rearrangement of gp41 trimers drivers membrane fusion

Question 16

What ligand blocks CCR5 HIV?

Answer 16

• RNTES

- MIP-1a/b

Question 17

What ligand blocks CXCR5

Answer 17

SDF-1

Question 18

What functional mutation protects against HIV-1 ?

Answer 18

CCR-5 delta32

Question 19

What functional mutation protects against HIV2?

Answer 19

SDF-1

Question 20

What is the tropsm of CCR5 and CXCR4?

Answer 20

M (Macrophage) and T (T-cell) Trophic respectively

Question 21

Which of the HIV types induce syncythium ?

Answer 21

CXCR4

Question 22

Which of the HIV types is morep athogenic?

Answer 22

CXCR4

Question 23

What is the pathogenesis of HIV from Mucosal exposure to spread infection?

Answer 23

• Mucosal exposure to HIV1
• Selective infection by R5 strain
• HIB binds to dendritic cell by DC-SIGN
• Transport of virus to regional lymph nodes
• Spread of infection to activated CD4+ T cells
• Entry of virus infected cells into bloodstream
• Dissemination

Question 24

What is the process of reverse transcription?

Answer 24

• Converts viral genomic RNA into proviral cDNA

- Adds a U3 to the 5’ LTR and a U5 in the 3’ LTR

Question 25

Where can the virus integrate its DNA?

Answer 25

Resting and terminally differentiated Cells

Question 26

What is the function of the 5' LTR

Answer 26

- It acts as HIV gene promoter - Increase expressed in response to Tat protein - Silences HIV expression soon after initial replication - Responds to cellular proteins during T-cell activation

Question 27

What molecules are important for T-Cell activation and how does it relate to HIV?

Answer 27

NFkB and NFAT are important molecules to T-Cell activation in performing immune function. These signals also activate integrated HIV genome by acetylating histones to open up DNA.

Question 28

What is the TAR RNA element?

Answer 28

It is the binding site for Tat to activate production of transcripton?

Question 29

That is the RRA?

Answer 29

It is the Rev-responsive RNA element, regulator of structural gene expression

Question 30

What is the function of Rev?

Answer 30

It stabilize and transports unspliced and partially spliced RRE+ HIB RNA to the cytoplasm to help express structural proteins This is the early expression (regulatory and accessory proteins)

Question 31

What i the accessory proteins for?

Answer 31

It is not important for replication but modulates pathogenesis of the virus

Question 32

What is the function of Tet

Answer 32

Increases HIV gene transcription

Question 33

What are some proteins involved in HIV pathogenesis (Accessory proteins)?

Answer 33

Vif, Vpr, Vpu and Nef

Question 34

What is the function of Vif?

Answer 34

Blocks APOBEC3G proteins which is a cell defence targeting single stranded cDNA to promote infectivity of cell free virus

Question 35

What is the function of vpr?

Answer 35

Nuclear import of cDNA, cell growth arrest and weak transcription transactivation

Question 36

what is the function of Vpu?

Answer 36

- Regulator of particle release and Env processing - Degrades MHC-1 and CD4 (via proteosome and lysosomal degradation) - Antagonizes TETHERIN

Question 37

What is the function of Nef

Answer 37

Down-regulate cell MHC-1 and CD4

Question 38

What is the function of TRIM5a?

Answer 38

Destabilization of the viral capsid

Question 39

What is the function of APOBEC3G

Answer 39

Lethal hyper-mutations

Question 40

What is the function of tetherin

Answer 40

Inhibition of virus release

Question 41

How many % of our genome are of retroviral origin?

Answer 41

8%

Question 42

Where does HIV particle mature?

Answer 42

After budding, Protease activity of Gag-Pol precursor protein causes cleavage of the polyproteins into individual proteins

Question 43

Where are the main latent HIV reservoir located?

Answer 43

T central and Transitional memory T cells