Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup a infection and identify a fusion intermediate.

Fusion proteins of enveloped viruses categorized as class I are typified by two distinct heptad repeat domains within the transmembrane subunit. These repeats are important structural elements that assemble into the six-helix bundles characteristic of the fusion-activated envelope trimer. Peptides derived from these domains can be potent and specific inhibitors of membrane fusion and virus infection.

Receptor-activated binding of viral fusion proteins to target membranes.

This chapter describes three assays to monitor receptor-induced association of the envelope glycoprotein (EnvA) of avian sarcoma/leukosis virus (ASLV) with target bilayers: (1) the original assay for monitoring binding of the EnvA ectodomain (EnvA-PI) to target membranes (liposomes), (2) a modified and miniaturized EnvA-PI-liposome binding assay, and (3) an assay to measure binding of intact sarcoma/leukosis virus subtype A (ASLV-A) virus particles to target membranes. These assays are also useful for studying other receptor-activated viral fusion proteins. When one viral glycoprotein and one “simple” host cell receptor are involved, it should be possible to develop assays directly analogous to those described above for studying Tva-induced binding of the EnvA ectodomain (EnvA-PI) to target membranes.

The avian retrovirus avian sarcoma/leukosis virus subtype A reaches the lipid mixing stage of fusion at neutral pH.

We previously showed that the envelope glycoprotein (EnvA) of avian sarcoma/leukosis virus subtype A (ASLV-A) binds to liposomes at neutral pH following incubation with its receptor, Tva, at >or=22 degrees C. We also provided evidence that ASLV-C fuses with cells at neutral pH. These findings suggested that receptor binding at neutral pH and >or=22 degrees C is sufficient to activate Env for fusion.