Negative-strand (NS) RNA viruses comprise many pathogens that cause serious 
diseases in humans and animals. Despite their clinical importance, little is 
known about the host factors required for their infection. Using vesicular 
stomatitis virus (VSV), a prototypic NS RNA virus in the family Rhabdoviridae, 
we conducted a human genome-wide siRNA screen and identified 72 host genes 
required for viral infection. Many of these identified genes were also required 
for infection by two other NS RNA viruses, the lymphocytic choriomeningitis 
virus of the Arenaviridae family and human parainfluenza virus type 3 of the 
Paramyxoviridae family. Genes affecting different stages of VSV infection, such 
as entry/uncoating, gene expression, and assembly/release, were identified. 
Depletion of the proteins of the coatomer complex I or its upstream effectors 
ARF1 or GBF1 led to detection of reduced levels of VSV RNA. Coatomer complex I 
was also required for infection of lymphocytic choriomeningitis virus and human 
parainfluenza virus type 3. These results highlight the evolutionarily conserved 
requirements for gene expression of diverse families of NS RNA viruses and 
demonstrate the involvement of host cell secretory pathway in the process.