Virology Flashcards
what types of organisms are HIV 1 and HIV 2
zoonotic organisms
how are viruses classified
by phenotypic characteristics
- morphology
- nucleic acid type
- mode of replication
- host organisms
- type of disease they cause
what are the 2 main schemes for classification of viruses
- international committee on taxonomy of viruses
- Baltimore
what hosts can hiv infect
only infects humans and great apes
what is the order of hiv in taxonomy
virales
- small microscopic capsule enclosing genetic material (2 copies of ssRNA)
What is the family of hiv in taxonomy
retroviridae
- HIV is a retrovirus (RNA and reverse transcriptase)
- Reverse transcriptase converts RNA into cDNA which integrates into host genome
what is the subfamily of hiv in taxonomy
orthoretrovirinae
- virion that is spherical and infects vertebrates
what is the genus of hiv in taxonomy
lentivirus
- slow viru
- takes years to replicate enough to cause symptoms in host
what is the species of HIV in taxonomy
human immunodeficiency virus type 1 and 2
- degrades immune system
- results in secondary infection (AIDs)
what does the hiv structure consist of
- 2 copies of ssRNA
- reverse transcriptase
- p24 capsid protein (gag)
- p17 matrix protein
- lipid envelope
- trimeric envelope (spike)
- host cell proteins (cd80)
outline the roles of gp120
- enables infection (receptor binding)
- ability to contact multiple receptors sequentially - receptor interaction through protein and carbohydrate bits of gp120
- evades host immune response
- determines cellular tropism (coreceptor binding)
- assists viral dissemination (app receptor binding and induction of apoptosis)
outline the roles of gp41
- enables infection (conformational change)
- evades host immune response
- permits oligomerisation
- extensive cell signalling via cytoplasmic region
describe the properties of the hiv envelope complex
- trimeric
- assembled as gp160 in golgi
- transported to surface membrane as trimer
- 7-20 trimers per virion
- fragile
- very difficult to reproduce trimeric env 3d structure for vaccine
describe the hiv clades
- when hiv replicates, mutations occur in env and gag genes
- 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 - recombinants also occur between env/gag genes of different clades called circulating recombinant forms
describe the clinical and diagnostic relevance of hiv clades
- some evidence of genotypic attributes
- non subtype B isolates preferentially tranmitted by MSM/iv drug use
- subtype C preference is heterosexual transmiss9on - ARV drugs developed against clade B isolates, but show cross clade efficacy
- some diagnostic tests may not detect CFFs, group 0 and rarer groupings
- 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
describe the importance of the HIV envelope
- interaction of hiv 1 envelope glycoprotein gp120 awith CD4 defines cellular tropism
- structure of trimeric envelope complex explains aspects of immune evasion
- constant mutation of env gene makes it hard for humoral response to control hiv and to develop effective vaccines
- but blabs raised against gp120/41 during natural infection are a major determinant of protection
- use of VRC01 (gp120 bNAb against CD4 binding site) in phase III trials
outline the core structural proteins
- gag gene encodes p53 precursor
- p53 cleaved by hiv protease to p17, p24 and smaller proteins
- p24 oligomerises form capsid and protects viral RNA
- very immunogenic and is a key diagnostic enzyme
- used in vaccines to induce CD8 and CTLs - p17 associates with lipid bilayer of viral membrane and coats its inner surface
- NCP7 is a nucleocapsid protein that coats and protects the viral RNA during transport to new virions
describe the role of hiv reverse transcriptase
- builds first dna strand using viral RNA as a template in polymerase active site
- then degrades original RNA strand in nuclease active site
- builds second, complimentary dna strand to first in polymerase active site
what are the reverse transcriptase target of ARV drugs
- nucleoside/nucleotide RT inhibitors
- non nucleoside RT inhibitors
describe the role of hiv integrase
- splices viral dna to form human chromosome
- 4 identical copies of integrase grab the 2 ends of viral dna to form intasome
- intasome binds to cellular dna joining viral dna, to form cellular dna
describe the role of hiv protease
- expressed from pol precurosr (p160) first, then cleaves RT and IN from p160
- Protease also cleaves gag precursor (p53)- key target
- crucial in viral transcription, replication and assembly
- has led to development of protease inhibitor drugs
- all act like protein chains and bind very tightly to active site of protease
give examples of the regulatory proteins and their role
- Nef- down regulates CD4 and MHCI and allows infected cell to hide from immune surveillance
. tat- promotes transcription of viral RNA to DNA
name the 7 stages of the HIV lifecycle
- Binding (attachment)
- fusion
- reverse transcription
- integration
- replication
- assembly
- budding
outline the first stage of the hiv lifecycle
- hiv binds and attaches
