HIV - Infection control Flashcards
How is HIV primarily transmitted
Sexual intercourse
When is HIV transmission at its highest likeliness
In the first month of infection or when newly infected individual is asymptomatic
Characteristics of primary HIV infection illness
- Asymptomatic
2. Unaware of infection
Why does HIV develop resistance to immune system
Because it mutates every time it reproduces
What are retroviruses
Enveloped viruses
What are the four major features of HIV
- Transmitted through sexual intercourse
- Remains inactive for a long time (carries on spreading it)
- Bad at reproducing itself accurately (mutations 50% of the time)
Describe the classification of HIV
- Retroviridiae -> Orthoretroviridae -> Lentivirus -> Primate Lentivirus group -> HIV -1 and HIV-2
What is reverse transcription
Viruses have reverse transcriptase enzymes which can turn their viral RNA into DNA when they take over host
What is a special feature of the lentivirus
Lenti = slow
Lentivirus has a SLOW incubation period
Did HIV-1 and 2 come from the same source
No, from different sources
What are the three types of HIV virus found in the world
M (main)
O (Outlying)
N (new)
What are the main sub-groups of M, O and N
CLADES
Clade B - predominate in Europe and USA
Clade A - west central africa
Clade C - South africa
Why is the acknowledge of clades important
Because different treatments may be required for treating the different clades (may only work for one clade and not another)
Define attachment
Viral and cell receptors
Define cell entry
Only central viral core carries nucleic acid and some associated proteins enter host cell
Describe the interaction of viruses
Use cell materials for replication
How do viruses replicate
Localise in nucleus, cytoplasm or both: production of progeny viral nucleic acid and proteins
Describe the assembly of viruses
Occurs in nucleus or cell membrane or cytoplasm
How are viruses released from a cell
Bursting open or exocytosis from the cell over time (latter is HIV)
Role of CD4
Recruits and facilitates maturation of B antibodies producing cells and T CD8 killer cells
What Interleukins are produced by TH1
4,5,10,13
What interleukins are produced by TH2
IFN alpha and TNF
How does HIV effect the immune system
Kills CD4 by uncontrolled activation and then apoptosis (less CD8, NK cells, neutrophils etc are produced)
Describe the vision structure
Nucleic acid in centre
Vision associated polymerase wrapped around acid
Protein cashed surrounds nucleic acid
Lipid envelope envelopes protein cashed
Spike projections protrude from lipid envelope
Describe the process of CD4 cell destruction
- HIV fuses to CD4 receptor and passes contents into cell
- Viral cashed is uncoated and enzymes and nucleic acid are released
- Reverse transcriptase RNA converted to DNA
- Viral DNA integrated into cells by integrate enzymes
- When infected cell divides, viral DNA read and transcribed and long chains of viral proteins are made
- Viral RNA spliced and protein chains cleaved and reassembled into individual proteins that recombine to form a virus
- Budding here causes immature virus to be pushed out of the cell taking some membrane with it
- Maturation
What receptors does CD4 bind to on the virus
Gp160 (made of gP120 + 41)
What genetic trait is preserved in all primate lentiviruses
The interaction between CD4 and gP120
How does binding of gP120 to CD4 affect the recpetor
GP120 undergoes conformational change
What can mutations in CCR5 do
Influence risk of infection
How long is the HIV viral RNA
9KB
What genes does the viral RNA encode for
9:
Gag, Pol, Env, Tat, Rev, Nef, Vif, Vpr, Vpu
What genes are essential for viral infectivity
Gag, Pol, Env, Tat, Rev
Role of Pol
Encodes the enzymes, reverse transcriptase, integrate and protease
Role of Env
Encodes the envelope proteins
Role of Nef
Increases infectivity
Role of Tat
Contributes to viral replication. Enhances production of host transcription factors
Which cells become infected by the HIV virus
CD4 T cells Macrophages Astrocytes Renal epithelial cells Brain endothelial cells
What CD4 is infected early on
CD45RO
What CD4 cells are infected later on
CD45RA when infected by X4 virus
When are dendritic cells infected by HIV
Early on as they trap the virus via DC-SIGN and transport virus to lymph nodes to infect T cells
Describe the process of HIV infection from the outside world
- Virus enters mucosa
- Single founder virus enters
- Local infection in mucosal macrophages
- Migrate to local lymph node to present antigen to T cells
- Virus macrophage infects T cells and more T cells which leave lymph nodes
Describe the effect of HIv on the humoural response
- Slow to develop effectively
2. Envelope glycoprotein (Gp120) is poorly immunogenic and has high genetic diversity
Effect of HIV on cell-mediated immunity
CD8:
- CTLs against HIV form early decline in virus
- CTL responses become quantitatively and qualitatively poor
- Virus escapes from CTL response through mutations
CD4:
Infected and don’t proliferate
What are long-term non-progressors
Heterogeneous groups of individuals that don’t progress to AIDS
Don’t show signs of AIDS after 7 years infection (CD4 count greater than 600 cells)
How does the CD4 T cell number die
- Very few are killed directly by the virus/infection
- Apoptosis as CD4 cells rapidly proliferate initially in response to virus (tries to maintain homeostasis in body as HIV activates too many CD4 cell than necessary)
- Decreased production due to CD34+ progenitors in the bone marrow being infected and disruption to environment in thymus)
- Redistribution of CD4 from periphery to lymphoid
- Bystander cell killing
What is bystander cell killing
Gp120 binding to CD4 increases cell apoptosis
How does HIV effect NK, neutrophils and macrophage function
Decreases it
How does HIV effect B cells
Enhanced activation and decreased proliferation resulting in an increased nonspecific Ab production
How does HIV effect T helper cells
Decreased TH1 response
Increased TH2 response
What are the reservoirs of HIV in th body
- Genital tract
- CNS
- GI tract
- Bone Marrow
Cells:
Macrophage
Microglia
Resting T cells