Lec 25 - Bloodborne viruses: HIV and AIDS

Question 1

When was HIV first discovered and where? What were the previous names before ‘HIV’?

Answer 1

• 1981 in homosexual male clusters with pneumocystis pneumonia and Kaposi’s sarcoma in Los Angeles, California and New York
• Lymphadenopathy associated virus, human T cell lymphotropic virus, AIDS associated retrovirus

Question 2

How many are infected with HIV and which population has the most (2022)?

Answer 2

39 million
Mainly adult women

Question 3

When was HIV-2 discovered and how is it related to HIV-1?

Answer 3

1986 in west Africa
50-60% similarity with HIV-1; closer related to SIV in macaques

Question 4

List the classification, structure of HIV’s genome and what it encodes

Answer 4

• Baltimore group 6 = enveloped sstranded (+) RNA virus with DNA intermediate; 2 copies of RNA
• RdDp or RT
• Structural = gag, pol,env
• Regulatory = tat, rev
• Accessory = vpu, vpr, vif, nef

Question 5

Describe the steps in HIV’s replication cycle

Answer 5

1. Fusion and entry = CD4 receptor and CXCR4/CCR5 coreceptor
2. RT of vRNA to dsDNA in cytoplasm
3. Import vdsDNA to nucleus
4. Integration of DNA into chromosome by viral integrase = provirus
5. Transcription of viral mRNA by RNA pol 2 and export from nucleus
6. Unspliced RNA = genomic RNA; spliced mRNA = translation
7. Assembly and budding
8. Viral protease cleaves structural polyprotein to mature gag = virion

Question 6

Which body secretions contain the most HIV?

Answer 6

Plasma and CSF

Question 7

How does HIV-1 diversify?

Answer 7

• High mutation rate bc low RT fidelity
• Retroviral recombination by template switching
• Host immune selection

Question 8

How does HIV initially enter tissues via mucosal surfaces?

Answer 8

• DCs and Langerhan cells in mucosa with ICAM-3 bound by HIV’s DC-SIGN glycoproteins
• Infected DCs allow HIV to disseminate and avoid anti-viral immunity

Question 9

What are the 2 strains of HIV-1?

Answer 9

1. T cell tropic X4 strain = CXCR4 coreceptor
2. Macrophage tropic R5 strain = CCR5 coreceptor

Question 10

When is HIV most transmitted?

Answer 10

Acute infection in first few weeks with big spike in viral RNA

Question 11

How does HIV affect the immune system?

Answer 11

• Loss of CD4+ T cells
• Accelerated thymic loss = regenerative failure of T cells by HIV infecting thymic precursors
• Cell death = gut mucosa then lymph nodes with fibrosis from inflammation

Question 12

Describe the 3 phases of HIV/AIDS

Answer 12

1. Eclipse phase (0-3wks) = initial infection, systemic by nodes, IFN response, viral reservoir established, gut mucosa destruction
2. Acute phase (3-9wks) = detect in blood, flu symptoms, CTL response, seroconversion = antibodies,
3. Chronic phase (6+mnths) = set point established, CD4+ T cell loss, chronic inflammation, AIDS

Question 13

What is the difference between a high and low set point in the chronic phase of HIV?

Answer 13

Higher set point = fit virus, CTL escape, immune dysfunction, high inflammation

Lower set point = poor virus, strong immune response by specific HLA types and CCR5-delta32 heterozygosity, low inflammation

Question 14

What are the 2 most commonly seen complications/diseases of HIV?

Answer 14

Pneumocystis pneumonia and oesophageal candiasis

Question 15

Compare HIV’s half life in blood vs other compartments

Answer 15

Blood = half-life of 6hrs
Other = latent infection half life 8.5 days, defective virus half life 145 days, long lived DCs half life 14.1 days

Question 16

How does HIV effect lymphoid tissue?

Answer 16

• Progressive dmg to node germinal centres
• Connective tissue replacement of cell population
• Increased viraemia and decreased immune capacity

Question 17

List some AIDS defining conditions

Answer 17

• Candidiasis of bronchi, trachea, oesophagus, lungs
• CMV disease esp retinitis
• Kaposi’s sarcoma (KS) (HHV-8)
• TB
• Pneumocystis jirovecii pneumonia
• Toxoplasmosis of brain