Abstract: The aim of this study was based on experimental infection via the pathogenic injections and natural infections by Yellow-head Virus (YHV). Whiteleg shrimp (Litopenaeus vannamei) were experimentally infected with YHV by either injection or co-habitation with YHV-injected shrimp. Thereafter, YHV load, L. vannamei Toll (LvToll) mRNA and LvToll protein level in gills of moribund and survived shrimp from both groups were determined. All shrimp of the YHV-injected group died within 3 days post-injection and 80% of co-habitation group died within 14 days, with 20% surviving to day 30. Moribund and survived shrimp gills were isolated and analyzed to determine YHV load and LvToll expression. Tissue was also assessed to determine LvToll protein level using an immunofluorescence method. Viral load and levels of LvToll and LvToll in moribund shrimp from co-habitation group were significantly higher than were those of moribund shrimp from YHV-injected group. Survived shrimp from co-habitation group had a significantly lower viral load and lower levels of LvToll and LvToll than the moribund shrimp of the same group. It suggests that mRNA and protein levels in shrimp following an infection by a particular pathogen could differ depending on the route of infection. As the co-habitation method of inducing infection is considered a natural mode of infection, this study also suggests that during natural YHV infection in penaeid shrimp, the up-regulation of LvToll does occur; whether this response is responsible for some degree of protection against mortality caused by YHV infection requires further study.