ABSTRACT. Five previously analyzed white spot syndrome virus (WSSV) strains from northwest Mexico, differing in their genome architecture as well as in virulence, were selected (high virulence JP and LG strains; moderate virulence GVE and DIV strains; and low virulence LC10 strain) to evaluate pathogenesis response in vitro. Expression of phagocytosis-activating protein PAP, manganese superoxide dismutase MnSOD and peroxiredoxin PRX, and two genes of immediate-early expression (IE1 and WSSV304) were measured by qPCR in a primary hemocyte cell culture from Penaeus vannamei at 1, 3, 6, 12, and 24 h post-infection (hpi). PAP expression was significantly higher at 1 and 3 hpi, and JP and LC10 strains induced the highest expression. The response of MnSOD was high at 1 hpi, and a significant increase in PRX expression was detected at 3 hpi, probably due to the occurrence of an oxidative burst; expression levels of MnSOD and PRX were significantly higher at 1 and 3 hpi, respectively, induced by the LG strain (high virulence), suggesting an acute response. In general, expression of most immune-related - genes decreased after the initial hours of infection. Expression levels of IE1 and WSSV304 were exceptionally high at 1 hpi in almost all five WSSV analyzed strains, confirming their efficient mechanism for replication and viral fitness. The results of this study do not show an accurate link between the genome size and WSSV virulence of the strains, albeit the strain with the smallest genome showed the highest virulence. All strains induced an early immune response in heterogeneous ways.