Membrane virus host range mutations and their uses as vaccine substrates

DETAILED DESCRIPTION What is claimed is: 1.
A genetically engineered Arbovirus comprising, a transmembrane glycoprotein with a deletion of one or more amino acids in a transmembrane domain wherein, said virus is capable of infecting and producing progeny virus in insect cells, wherein said engineered Arbovirus has an ability to infect mammalian cells but a reduced ability to replicate therein relative to wild type virus.
2.
The genetically engineered Arbovirus of claim 1, wherein the insect cells are mosquito cells.
3.
The genetically engineered Arbovirus of claim 2, wherein the mosquito cells are Aedes ablbopictus cells.
4.
The genetically engineered Arbovirus of claim 1, wherein said virus produces at least 1,000 fold more progeny virus when infecting insect cells than when infecting mammalian cells.
5.
The genetically engineered Arbovirus of claim 4, wherein said virus produces at least 10,000 fold more progeny virus when infecting insect cells than when infecting mammalian cells.
6.
The genetically engineered Arbovirus of claim 1, wherein the transmembrane glycoprotein has a deletion of nine or more amino acids in a transmembrane domain.
7.
The genetically engineered Arbovirus of claim 1, wherein the genetically engineered Arbovirus is a genetically engineered Togavirus, Flavivirus or Bunyavirus.
8.
The genetically engineered Arbovirus of claim 7, wherein the genetically engineered Togavirus is a genetically engineered Alphavirus.
9.
The genetically engineered Arbovirus of claim 8, wherein said transmembrane glycoprotein is glycoprotein E1, or glycoprotein E2.
10.
The genetically engineered Arbovirus of claim 9, wherein the genetically engineered Alphavirus is a genetically engineered Sindbis virus.
11.
The genetically engineered Arbovirus of claim 10, wherein said genetically engineered Sindbis virus is the TM16 virus.
12.
The genetically engineered Arbovirus of claim 10, wherein said genetically engineered Sindbis virus is the .
DELTA.
K391 virus.
13.
The genetically engineered Arbovirus of claim 10, wherein said genetically engineered Sindbis virus is the TM17 virus