HIV Part 1 Flashcards
AIDS (Aquired Immunodeficieny Syndrome)
- HIV + Opportunistic infections
- Immunocompromised individuals
- Low levels of CD4 T helper cells
HIV (Human Immunodeficiency Virus)
- HIV-1 and HIV-2 subtypes
- Vaccines against all sub types is important
- High mutation rates- variants
- Variants- changes to which cell type they infect
- All similar structure and replication process
HIV structure
- Retrovirus (Lentifamily)
- 2 single stranded RNA- bound by molecule of reverse transcriptase
- In genome - p10 protease and p32 integrase
- Surrounded by nucleocapsid - inner layer of protein p24, outer layer of protein p17
- > p24 = core antigen capsid protein
- > both: Gag (group specific antigen) polyprotein complex)
- Outer most portion- lipid membrane derived from host cell
- > contains gp120 and gp41 = envelope proteins
What are its viral envelop proteins?
g120
gp41
What proteins make up the nucleocapsid?
Inner = p24
Outer=p17
p24 and p17 form what complex?
GAG polyprotein complex
What proteins what in the genome of HIV?
p10- protease
p32- integrase
What does GAG encode for?
- Created as a larger molecule =p53 = GAG precursor polyprotein
- To become function its broken down by protease to produce -Structural capsid proteins
- > p24 = core antigen capsid protein
p17
Matrix protein - 131 amino acids
p7
Nucleo-capsid protein - 55 amino acids
Role of the GAG protein
- outermembrane
- assemby of new HIV virus particles
- Brings viral RNA and viral proteins and host proteins together
- triggers process of forming new virus particles
- breaks awat from host cell surface
- infect other cells
What side chains are found on gp120?
Glycans
What receptor does HIV target and where is it expressed?
- CD4+ receptor
- On CD4+ T helper cells, some on monocytes and dentritic cells
2 stages of HIV viral infection
- Binding - gp120 (viral envelope) to CD4+ receptor
- Fusion
What type of receptors are CD4+ Receptor
Glycoproteins
* Co-receptor of T cell receptor (TCR)
Upon viral recognition of CD4+ R, what it secreted to fight off infection?
- B cells
- T killer
- CD4+ T helper (HIV target)
Normal function of CD4
- Major histocompatability complex II (MHCII) molecules on antigen presenting cell
- Present antigen (piece from bacteria)
- CD4+ and TCR bind to MHCII at different region
- Brings it closer- enabled Lck kinase to phosphorylate ITAMS on CD3 complex on TCR.
- Phosphorylated ITAMS recruit ZAP70 enymze
- Activates downstream signal transduction via tyrosine phosphorylation in T cell
- > phorphorylation of proteins
- NF-Kappab (NK-kb) activation
- Leads to T cell activiation- immune response against presented antigen
Possible diagram question- Life Cycle of HIV
1). Binds to CD4 +ve cells through gp120 to CD4; interactions between virus and chemokine co-receptors.
2). Nucleocapsid enters the cell, unfolds, releasing viral RNA, which is reverse-transcribed to DS DNA.
3). The viral DNA integrates in the host genome, where it lies dormant as a provirus.
4). Following cell activation, viral DNA directs the transcription of viral RNA.
5). Viral proteins are translated from the RNA.
6) Viral proteins and single-stranded viral RNA assemble to form new viral particles.
7). Virus buds from the cell, picking up some of cell membrane, complete viral particles can infect other cells.
When gp120 binds to CD4+ what other co-receptor is involved?
Chemokine co-receptor
What is the virus called when its genetic material integrates with host genome?
Provirus
The provirus is said to be what before activated?
Dormant
What is the specific chemokine co-receptor associated with CD4+TCR?
CCR5
Hijacks immune cell- HIV circumvents normal Dendritic Cell -T cell inter
Explain the viral strategy for efficient transmission of viral particles upon dendritic infection?
- Dendritic shoot out thin appendages - filopodia
- Rearrangement of actin filaments
- Relatively fast
- Carries the viral particle to T cells
- Waving arc motion
- Efficient viral transmission
Old Model HIV Binding
Explain HIV binding
- gp120 binds to co-receptor CD4+ on TCR
- gp41 bind to a second protein = chemokine co-receptor on TCR
- 2 types of co-receptor depending on HIV Variant