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Receptors by Mind Map: Receptors

1. What are the entry basics?

1.1. pH independent

1.1.1. .

1.1.1.1. gp41 and gp120 interact with CD4

1.1.1.1.1. CD4 Ab potent anti-HIV compounds

1.1.1.1.2. gp41 fusion inhibitors (T-20, intercalates with alpha helices to prevent conformational change)

1.1.1.2. CCR5 or CXCR4 coreceptor on mb

1.1.1.2.1. more promising targets

1.2. pH dependent

1.2.1. acid activated

1.2.1.1. 1. attachment 2. endocytosis 3. early endosome 4. late endosome (pH 6) 5. fusion

1.2.1.1.1. HA

1.2.1.1.2. sialic acid

1.3. receptors -> cell-, species-, tissue tropism

2. NiV and HeV: cloning receptors of emerging viruses

2.1. host

2.1.1. Bats (asymptomatic HeV NiV) 47% QLD bats seropositive

2.1.2. Pigs (Ni) low mortality 1-5% 100% transmission (resp illness)

2.1.3. horses (He) high mort

2.1.4. humans (He, Ni) high mort, low transmission

2.2. safe studies

2.2.1. need BS level 4 (few facilities)

2.2.1.1. microarray

2.2.1.1.1. permissive

2.2.1.1.2. non-permissive

2.2.1.1.3. fusion assay

2.2.2. non-BSL4 -

2.2.2.1. 1 fusion assay (NiV G/F protein production in permissive cell lines)

2.2.2.1.1. syncytia/multinucleation (mechanistically identical to viral fusion)

2.2.2.2. 2 pseudotyped virus

2.2.2.2.1. VSV - delete receptor - put He/Ni receptor on

2.3. (G or HN) binds to (measles-CD4, Sendai-sialic acid)

2.4. F protein directs fusion

3. tissue and species tropism

4. HIV: blocking entry