VPI Biology and Physiology 2 Flashcards
How does HIV onvercome the small nucleic acid load in capsid…?
1) Multiple ‘reading frames’ allows virus to transcribe same DNA into different protein seq,
Use of Polyproteins (large precurosers that are cleaved to form functional smaller proteins)
Use of single Capsid protein
(p24 capsid protein hex,dim,pentamers)
How does the use of polyproteins save genetic space
Allows for more compact genome by eliminating ( genetic features e,g promoters)
HIV has 3 genes Encoding polyproteins
1) ENV gp-120 and gp41 (attachment and fusion (release))
2) POL ( Reverse transcriptase)
3) GAG ( Capsid & matrix proteins)
HIV-1 Tropism
HIV enters cells via cellular receptor and co-receptor
Co receptors on:
i) macrophages
ii) T-lymphocytes
i) CCR5
ii) CXCR4
Early HIV and Late HIV
Early hiv infects macrophages (CCR5) during later infection it infects CD4+ T-lymphocytes (CXCR4)
Rapid progression to AIDS is associated with..?
With the switch in HIV-1 Tropism from macrophages to CD4+T cells
HIV Entry : attachment
Gp120 Binds to CD4 on host cell
Conformational change in gp120 allows interaction with co-receptor CCR5 or CXCR4
Hiv entry 2: Fusion
Further conformational changes results in gp41 Fusogenic tip insertion into cell -> Fusion of viral and cellular membranes
Enfuvirtide : Fusion inhibitor : MOA
Inhibits fusion process preventing virus from infecting cell
HIV-1 Entry inhibitors (3)
1) gp120-CD4 binding
2) gp120-coreceptor binding
3) gp41-mediated membrane fusion
Natural resistance to HIV infection
CCR5 not being displayed (resistance)
HIV uncoating after uptake (2 developmental stages are…?)
Reverse transcription compelx (RTC)
Pre-intergration complex (PIC)
Retroviral RT: 3 biochemical activiteis
RNA-dependent DNA polyermase
RNAse H (nuclease)
DNA-dependet DNA polymerase activity
What occurs in the retroviral Reverse transcripatase activiteis?
1) RT of RNA -> DNA
2) RNA is cleaved and degraded
3) use First strand DNA to complete (then intergrate into host genome)
Reverse transcriptase (RT) inhibitors example
zidovudine
Intergration of HIV viral DNA
Done by Intergrase (encoded by viral pol gene)
Intergrase inhibitors e.g and MOA:
Raltegravir
Targets intergrase viral DNA in the PIC
Replication occurs via
When DNA is copied viral DNA is copied aswell.
Assembly Budding and Maturation;
What does GAG encode..?
GAG gene encodes Structural proteins of the viral caspid (needs to be cleaved from polyprotein)
Cleavage of HIV results release of matrix proteins (MA, CA, NC, p6)
What are MA, CA, NC and p6?
And viruses that have not undergone full maturation by….. are ….?
MA - Matrix protein
CA - Capsid protein
NC - Nucleocapsid
p6 - intiates budding
Full maturation by proteolytic cleavage (HIV protease) are not infective
Protease inhibitors :
Bind and block the active site of HIV protease
All the classes of drugs against HIV infection;
Entry Inhibitors
Reverse transcriptase inhibitors
Intergration inhibitors
Protease Inhibitors
Examples of each class of drug; Entry inhbitors RT inhibitors Intergration inhibitors HIV protease inhibitors
1) Maraviroc
2) Zidovudine
3) Raltegravir
4) Saquinavir
