CSB351Y1 Lecture Notes - Lecture 43: Aids, Canarypox, Ritonavir
26 May 2018
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Lecture 43
HIV-1 Clades
• Group M (major) subdivided into clades (subtypes) since two viruses of different subtype can infect (hybid virus)
- Circulating recombinant forms (CRFs) – new strains not surviving long but infect more than one person (A/B)
• Transmission through body fluid – very high (blood, semen, genital secretions), high (milk) and low/no (saliva,
tears, urine, sweat, feces)
• Diagnostics
- ELISA – serum for HIV antibodies with antigen fixed to it (found in drug stores)
- RT-PCR in lab
- Western blot analysis in lab
- CD4/CD8 Tcell ratio – count t cells available in blood sample (tells how strong your immune system is)
◼ Combined with viral load test – measures level of HIV in blood (can show how well you respond to
treatment and chances of progression of HIV infection) viral load test is via RT-PCR
Antiretrovirals for HIV1
• Protease inhibitors (Ritonavir), nucleoside reverse transcriptase inhibitors (AZT), NNRTI (nevirapine), integrase
inhibitors, early entry/fusion (gp120 and 41) inhibitors, CCR5 receptor antagonists
• AZT first drug for AIDS patients (nucleoside analogues targeting reverse transcriptatse) – competitive inhibitor
blocking dNTP from binding to template, terminates elongation and inhibits RT not cellular DNA polymerase
- AZT has N3 (azido) on ribose so next base cannot be added to DNA chain and synthesis stops
- Has side effects (nausea, muscle wasting, headaches) due to causation of depleting intracellular TTP
- AZT treatment can damage bone marrow
• NNRTI id allosterially at ezye’s ative site
• Protease inhibitors (ritonavir) – prevents cleavage of gag protein and prevents maturation of virus particle
• Triple drug regiment (HAART) – combination of different drugs seemed to decline HIV particles in patients
(oiatio due to virus’ aility to utate)
- Protease inhibitor + RT inhibitor combination → highly active antiretroviral therapy (HAART)
• New trial RV144 in Thailand due to highest AIDS there (6% of Asia in Thailand, growing 8500 a day)
ALVAC-HIV
• vCP1452 is gene from vaccine used to protect canaries against canarypox virus
- vCP1452 uses canarypox virus to carry HIV envelop, core and regulatory protein
- Does not replicate in human cells but can enter.. proteins made can trick immune system into thinking that
host is infected with HIV and make CTLs (cytotoxic T lypmphocytes) that kill HIV cells
• AIDSVAX – consists of HIV-1 envelope gp120 making neutralizing antibody response
• Both are not efficacious on their own but when combined, prime-boost vaccine strategy were successful
Lentivirus expression vector
• Can infect nondividing cells while retrovirus only enter during cell division
• VSVG (vesicular stomatitis virus G protein) used instead of gp120 that can infect MANY cell types
• Not pathogenic, only essential elements required for integration are preserved
• 3 different constructs, 3 different plasmids
- CMV→gag,pol,rev→polA – packaging construct
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Hiv-1 clades: group m (major) subdivided into clades (subtypes) since two viruses of different subtype can infect (hybid virus) Elisa serum for hiv antibodies with antigen fixed to it (found in drug stores) Cd4/cd8 tcell ratio count t cells available in blood sample (tells how strong your immune system is) Combined with viral load test measures level of hiv in blood (can show how well you respond to treatment and chances of progression of hiv infection) viral load test is via rt-pcr. Azt has n3 (azido) on ribose so next base cannot be added to dna chain and synthesis stops. Has side effects (nausea, muscle wasting, headaches) due to causation of depleting intracellular ttp. Protease inhibitor + rt inhibitor combination highly active antiretroviral therapy (haart: new trial rv144 in thailand due to highest aids there (6% of asia in thailand, growing 8500 a day)
