HIV Part 1 Flashcards

1
Q

AIDS (Aquired Immunodeficieny Syndrome)

A
  • HIV + Opportunistic infections
  • Immunocompromised individuals
  • Low levels of CD4 T helper cells
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2
Q

HIV (Human Immunodeficiency Virus)

A
  • 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
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3
Q

HIV structure

A
  • 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
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4
Q

What are its viral envelop proteins?

A

g120
gp41

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5
Q

What proteins make up the nucleocapsid?

A

Inner = p24
Outer=p17

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6
Q

p24 and p17 form what complex?

A

GAG polyprotein complex

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7
Q

What proteins what in the genome of HIV?

A

p10- protease
p32- integrase

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8
Q

What does GAG encode for?

A
  • 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
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9
Q

p17

A

Matrix protein - 131 amino acids

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10
Q

p7

A

Nucleo-capsid protein - 55 amino acids

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11
Q

Role of the GAG protein

A
  • 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
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12
Q

What side chains are found on gp120?

A

Glycans

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13
Q

What receptor does HIV target and where is it expressed?

A
  • CD4+ receptor
  • On CD4+ T helper cells, some on monocytes and dentritic cells
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14
Q

2 stages of HIV viral infection

A
  1. Binding - gp120 (viral envelope) to CD4+ receptor
  2. Fusion
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15
Q

What type of receptors are CD4+ Receptor

A

Glycoproteins
* Co-receptor of T cell receptor (TCR)

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16
Q

Upon viral recognition of CD4+ R, what it secreted to fight off infection?

A
  • B cells
  • T killer
  • CD4+ T helper (HIV target)
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17
Q

Normal function of CD4

A
  • 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
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18
Q

Possible diagram question- Life Cycle of HIV

A

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.

19
Q

When gp120 binds to CD4+ what other co-receptor is involved?

A

Chemokine co-receptor

20
Q

What is the virus called when its genetic material integrates with host genome?

21
Q

The provirus is said to be what before activated?

22
Q

What is the specific chemokine co-receptor associated with CD4+TCR?

23
Q

Hijacks immune cell- HIV circumvents normal Dendritic Cell -T cell inter

Explain the viral strategy for efficient transmission of viral particles upon dendritic infection?

A
  • 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
24
Q

Old Model HIV Binding

Explain HIV binding

A
  • 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
25
# Old model HIV bonding M-tropic variant
**M-tropic variant** * gp41 brinds to **b-chemokine co-receptor** = **CCR5** * Present: CD4+ T cells, Monocytes and Dendritic cells
26
# Old model HIV binding T-tropic variant
**T-tropic variant** * a-chemokine co-receptor= CXCR4 * **Only on CD4 T cells** * Not expressed on monocytes * Not expressed on Dendritic cells
27
# HIV Binding (New model) Explain the new model for HIV model in detail?
* gp160= precursor fusion glycoprotein * >fuse viral and host membrane * Spike formation - trimer (3 molecules) of gp120 come together * Cleaved -> gp4(transmembrane) + gp120(surface) * gp120: binds to CD4+ co-receptor * >structural change, binds to chemokine receptor (CXCR4 or CCR5) * >Acitvates gp41 (high energy state) * >buried **fusion peptide** (linked amino acids) extends * Bridges gap between viral membrane and host cell membrane * For viral content to enter host cell
28
How can HIV entry be inhibited?
* Downregulating the expression of chemokine receptor expression * >reduces entry points for the virus * saturating chemokine receptors with their natural ligand-> chemokine * >prevent HIV entry
29
# Chemokine exression M tropic HIV susceptibility
* Binds to CCR5 chemokine receptor * Mutation -> CCR5(change)32 * >32 base pair deletions * Renders receptor non-functional * Protection to individuals against M tropic HIV variants * Virus difficulty entering cells that express mutated CCR5 receptor * Prevelant Europe and North Amerca * Rare in Indian populations
30
What is MIP-1a?
* Macrophage Inflammatory Protein 1alpha * Ligand to CCR5 * 1 in 5 Indians
31
T-tropic HIV variant susceptibility
* Binds to CXCR4 chemokine receptor * Ligand= SDF-1 (stromal cell derived factor-1) * Mutation leads to: Guanine -> Adenine (point mutation) * Present in 40% in Healthy Asian individuals * Interfers ability for the HIV virus to bind
32
Why is mutated CCR-5 gene results in delayed progression to AIDS?
* CCR5 - 2 alleles * >function/mutation * 10% of Northern Europeans- mutation - non functionable * delayed AIDs progression -ineffective binding M tropic variants
33
1% of caucasians have 2 copies of the CCR-5 gene mutated. What does this mean in terms of HIV infection? Consider expression of CXCR-4 in your answer.
* Resistant to HIV * As CCR5 is primary viral entry * But still express- CXCR4 (T tropic variant) * Suggesting M tropic variant is initial infection entry
34
35
How can be rapid progression of AIDs be determined?
Emergence of T tropic variant
36
Explain the steps of HIV replication in detail?
* Upon HIV entry into T cell -> nucleocapsid removed * Reverse transcriptase: Viral ssRNA -> dsDNA * >error prone process, 10mistakes/replication * >high mutation rate * dsDNA integrated into host genome (integrase) * >Provirus (dormant/latent) -inactive for long periods of time * RNA template degraded by Rnase H enzyme **T cell activation** * upregulation of NF-kb * >triggers initiation of virus production from provirus DNA * Transcribes into viral RNA-> (translated) Viral proteins * Assembled -> new virus particles that bud from the host cell * >acquires portion of host cell membrane * >**Viral envelope** * Cycle repeats to infect other cells
37
What is the role of the endoplasmic reticulum in the T cell?
* Processing and packaging of proteins * Glycosylation * >add carbohydrated molecules to protens * Significance to protein function, structure and stability
38
What are the 3 clinical course of HIV infection?
* Infection * the 'latent' stage * Development of AIDS
39
Development of AIDs graph
* progressive loss of CD4 T cell function * severe immune supression * susceptible to opportunistic infections
40
Infection
* Most people no symptoms immediately after infection * 15% : symptoms of influenza * >fever, malaise, aching muscles, soar throat, swollen lymph nodes * Development of swollen lymph nodes - no other clinical symptom identified * Production of antibodies against HIV antigen * >process called **seroconversion** * Detection of antibofies to HIV- test for infection
41
* asymptomatic * 33% swollen lymph nodes * 10 years (AIDs development) * Extremely variable
42
Development of AIDs is clinically defined by?
appearance of **major opportunistic infections** or by a drop in the **CD4 T cell count** to** below 200 cells/µl of blood**
43
AIDs symptoms
weight loss, night sweats, fever and diarrhoea
44
Opportunistic infection in HIV (AIDs)