Work with Katie Hooper his graduate student. Work just came out in Journal of Virology.
Hemagglutnin (HA): conform in one unit, then a cleavage. This is no longer the minimum energy conformation. This binds to sialic acid, it gets endocytosed. How to fuse with the membrane? For flu, this is a pH drop. Releases the HA spring.
Neuraminidase (NA) doesn’t seem necessary for viral entry. Rather, it binds sialic acid releasing it from attachment. Tamiflu binds NA. It was designed by structural means!
Find a mutation that leads to weak growth. Passage leads to better growth… mutation in HA! This leads to question of if NA can be used for binding.
It seems so! Mutation experiments.
Is HA needed for fusion? It seems like it should be– seems somewhat conserved between HIV and flu. Seems like it.
Does the mutant NA still cleave sialic acid? Yes. A little bit less cleaving, and a better binder. Tamiflu still works against it. This keeps the virus from infecting.