CSB351Y1 Lecture Notes - Lecture 42: Sooty Mangabey, Lymphadenopathy, Antigen-Presenting Cell
26 May 2018
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Lecture 42
• HIV1 (chimpanzees) and HIV2 both come from monkeys, cause of transmission due to bushmeat consumption
- HIV a descendant of SIV since they are closely resembling HIV (HIV2-SIVsm in sooty mangabey)
- HIV1 is more pandemic and virulent (SIVcpz in chimpanzees)
• 33.3M (36 in 2016) living with HIS, 22.5 million in Sub-saharan Africa (24.7 in 2006), 2.5 million children in 2004
Expression strategy of HIV-1
• Different mRNAs produced by HIV, involved in alternate splicing
• Regulatory proteins:
- Tat (transcriptional trans-activator) protein – for gene expression and replication, is an early nuclear
protein, activates transcription by binding to TAR and increase mRNA stability
- Rev (regulator of expression of viral) protein – post-transcriptionally stabilizes high molecular weight
mRNAs and transport them outside nucleus. Downregulates its own expression, tat and nef late in infection.
Rev binds to RRE, overriding negative effects of CRS (CRS prevents transport of RNAs out nucleus)
- Nef (negative effector) – determinant of pathogenicity (nef mice develops late stages of AIDS)
• Maturation proteins: vif, vpr, vpu
• Structural proteins: Gag, pol, env
Receptors
• gp120 attaches to CD4 receptors on certain cells (CD4 lymphocytes/T-helper cells and macrophage)
• Chemokine receptors (gp120, CD4 receptor and co-receptors (gp41) must be in place for HIV-1 to enter)
- CCR-5 expressed in monocytes and lymphocytes
- CXCR-4 (fusin) expressed only on T lymphocytes
- CCR-2 and CCR-3 serve as coreceptors
Fusion
• After Gp120 binds with CD4 to chemokine receptor, Gp120 released, Gp41 membrane insertion into host cell
membrane and is doing all the fusing (fusion domain)
- Gp120 is basically the anchoring protein, Gp41 is the insertion/fusion protein
• Transmission – sexual contact, blood, body fluids, perinatal exchange of fluids mother to child (vertical)
• Tropism – CD4+ T cells and macrophage lineage (monocytes, dendritic, microglial) are infected (antigen
presenting cells that are depleted when infected)
HIV infection
• Starts with acute HIV, followed by latency period lasting for years. virus depletes CD4+ T cells that patient
succumbs to opportunistic infections
• At acute phase, high amount of viral RNA replication but slow decrease in T cells
• At long latency period, the virus slowly gains hold while T cells keep decreasing
• Fullblown AIDS (increase in viral replication due to healthy/T cells to defend) → opportunistic disease → death
• Symptoms – early infection asymptomatic, few days-weeks → fever, headache, fatigue, enlarged lymph nodes
- Latency period – immune system broken, energy and weight loss, fevers and sweats, yeast infection, skin
rash, flaky skin, pelvic inflammatory disease, memory loss, herpes
- No cures but antiretroviral therapy that helps patients live normal lifespan but take antiretroviral everyday
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Document Summary
Lecture 42: hiv1 (chimpanzees) and hiv2 both come from monkeys, cause of transmission due to bushmeat consumption. Hiv a descendant of siv since they are closely resembling hiv (hiv2-sivsm in sooty mangabey) Hiv1 is more pandemic and virulent (sivcpz in chimpanzees: 33. 3m (36 in 2016) living with his, 22. 5 million in sub-saharan africa (24. 7 in 2006), 2. 5 million children in 2004. Expression strategy of hiv-1: different mrnas produced by hiv, involved in alternate splicing, regulatory proteins: Tat (transcriptional trans-activator) protein for gene expression and replication, is an early nuclear protein, activates transcription by binding to tar and increase mrna stability. Rev (regulator of expression of viral) protein post-transcriptionally stabilizes high molecular weight mrnas and transport them outside nucleus. Downregulates its own expression, tat and nef late in infection. Rev binds to rre, overriding negative effects of crs (crs prevents transport of rnas out nucleus)
