Table 1.

Strategies for construction of LAIVs.

Strategy	Mechanism of Attenuation
Cold-adaptation	Genetic mutations accumulated during cold-adaptation result in decreased viral replication at body temperature.
Deletion or truncation of NS1	The lack of interferon antagonist NS1 protein results in decreased viral replication in infected cells.
Deletion of M2 ion channel	M2-deficient influenza viruses replicates only in cells expressing M2 proteins but are highly restricted in normal cells.
Caspase-dependent cleavage of viral proteins	Cleavage of viral proteins by caspases activated during apoptosis of infected cells results in decreased viral replication.
Modification of HA cleavage site	The mutant viruses carrying elastase cleavage site in HA undergo restricted replication because of the absence of appropriate protease.
miRNA-mediated gene silencing	The viral genes carrying miRNA-targeted region are degraded in infected cells.
Codon deoptimization	Codon deoptimization results in downregulation of viral protein synthesis in infected cells.
Engineering of splicing elements	Modification of splicing elements in viral genes results in decreased production of the proteins in infected cells.