Virology

Question 1

what types of organisms are HIV 1 and HIV 2

Answer 1

zoonotic organisms

Question 2

how are viruses classified

Answer 2

by phenotypic characteristics
- morphology
- nucleic acid type
- mode of replication
- host organisms
- type of disease they cause

Question 3

what are the 2 main schemes for classification of viruses

Answer 3

1. international committee on taxonomy of viruses
2. Baltimore

Question 4

what hosts can hiv infect

Answer 4

only infects humans and great apes

Question 5

what is the order of hiv in taxonomy

Answer 5

virales
- small microscopic capsule enclosing genetic material (2 copies of ssRNA)

Question 6

What is the family of hiv in taxonomy

Answer 6

retroviridae
- HIV is a retrovirus (RNA and reverse transcriptase)
- Reverse transcriptase converts RNA into cDNA which integrates into host genome

Question 7

what is the subfamily of hiv in taxonomy

Answer 7

orthoretrovirinae
- virion that is spherical and infects vertebrates

Question 8

what is the genus of hiv in taxonomy

Answer 8

lentivirus
- slow viru
- takes years to replicate enough to cause symptoms in host

Question 9

what is the species of HIV in taxonomy

Answer 9

human immunodeficiency virus type 1 and 2
- degrades immune system
- results in secondary infection (AIDs)

Question 10

what does the hiv structure consist of

Answer 10

• 2 copies of ssRNA
• reverse transcriptase
• p24 capsid protein (gag)
• p17 matrix protein
• lipid envelope
• trimeric envelope (spike)
• host cell proteins (cd80)

Question 11

outline the roles of gp120

Answer 11

1. enables infection (receptor binding)
   - ability to contact multiple receptors sequentially
2. receptor interaction through protein and carbohydrate bits of gp120
3. evades host immune response
4. determines cellular tropism (coreceptor binding)
5. assists viral dissemination (app receptor binding and induction of apoptosis)

Question 12

outline the roles of gp41

Answer 12

1. enables infection (conformational change)
2. evades host immune response
3. permits oligomerisation
4. extensive cell signalling via cytoplasmic region

Question 13

describe the properties of the hiv envelope complex

Answer 13

1. trimeric
2. assembled as gp160 in golgi
3. transported to surface membrane as trimer
4. 7-20 trimers per virion
5. fragile
6. very difficult to reproduce trimeric env 3d structure for vaccine

Question 14

describe the hiv clades

Answer 14

1. when hiv replicates, mutations occur in env and gag genes
2. leads to genotypic groupings based on env/gag sequence
   - 9 major subgroups which have specific geographical locations
   - A- india, africa
   - B- Western Europe, Australia, america
   c- asia, africa, china
3. recombinants also occur between env/gag genes of different clades called circulating recombinant forms

Question 15

describe the clinical and diagnostic relevance of hiv clades

Answer 15

1. some evidence of genotypic attributes
   - non subtype B isolates preferentially tranmitted by MSM/iv drug use
   - subtype C preference is heterosexual transmiss9on
2. ARV drugs developed against clade B isolates, but show cross clade efficacy
3. some diagnostic tests may not detect CFFs, group 0 and rarer groupings
4. vaccines must be targeted at specific clades as boradly neutralising antibodies are hard to induce by vaccination
   - small subset of hiv + patients with low viral load do produce antibodies
   - isolated for potent passive immunisation

Question 16

describe the importance of the HIV envelope

Answer 16

1. interaction of hiv 1 envelope glycoprotein gp120 awith CD4 defines cellular tropism
2. structure of trimeric envelope complex explains aspects of immune evasion
3. constant mutation of env gene makes it hard for humoral response to control hiv and to develop effective vaccines
4. but blabs raised against gp120/41 during natural infection are a major determinant of protection
5. use of VRC01 (gp120 bNAb against CD4 binding site) in phase III trials

Question 17

outline the core structural proteins

Answer 17

1. gag gene encodes p53 precursor
2. p53 cleaved by hiv protease to p17, p24 and smaller proteins
3. p24 oligomerises form capsid and protects viral RNA
   - very immunogenic and is a key diagnostic enzyme
   - used in vaccines to induce CD8 and CTLs
4. p17 associates with lipid bilayer of viral membrane and coats its inner surface
5. NCP7 is a nucleocapsid protein that coats and protects the viral RNA during transport to new virions

Question 18

describe the role of hiv reverse transcriptase

Answer 18

1. builds first dna strand using viral RNA as a template in polymerase active site
2. then degrades original RNA strand in nuclease active site
3. builds second, complimentary dna strand to first in polymerase active site

Question 19

what are the reverse transcriptase target of ARV drugs

Answer 19

• nucleoside/nucleotide RT inhibitors
• non nucleoside RT inhibitors

Question 20

describe the role of hiv integrase

Answer 20

1. splices viral dna to form human chromosome
2. 4 identical copies of integrase grab the 2 ends of viral dna to form intasome
3. intasome binds to cellular dna joining viral dna, to form cellular dna

Question 21

describe the role of hiv protease

Answer 21

1. expressed from pol precurosr (p160) first, then cleaves RT and IN from p160
2. Protease also cleaves gag precursor (p53)- key target
3. crucial in viral transcription, replication and assembly
4. has led to development of protease inhibitor drugs
   - all act like protein chains and bind very tightly to active site of protease

Question 22

give examples of the regulatory proteins and their role

Answer 22

1. Nef- down regulates CD4 and MHCI and allows infected cell to hide from immune surveillance
   . tat- promotes transcription of viral RNA to DNA

Question 23

name the 7 stages of the HIV lifecycle

Answer 23

1. Binding (attachment)
2. fusion
3. reverse transcription
4. integration
5. replication
6. assembly
7. budding

Question 24

outline the first stage of the hiv lifecycle

Answer 24

1. hiv binds and attaches