The difference in CD4+ T cell immunity between high- and low-virulence Tembusu viruses is mainly related to residues 151 and 304 in the envelope protein

Abstract

Tembusu virus (TMUV) can result in a severe disease affecting domestic ducks. The role of T cells in protection from TMUV infection and the molecular basis of T cell-mediated protection against TMUV remain largely uncharacterized. Here, we used the high-virulence TMUV strain Y and the low-virulence TMUV strain PS to investigate the protective role for TMUV-specific CD4+ and CD8+ T cells. When tested in a 5-day-old Pekin duck model, Y and PS induced comparable levels of neutralizing antibody, whereas Y elicited significantly stronger cellular immune response relative to PS. Using a duck adoptive transfer model, we showed that both CD4+ and CD8+ T cells provided significant protection from TMUV-related disease, with CD8+ T cell conferring more robust protection to recipient ducklings. For TMUV, CD4+ T cells mainly provided help for neutralizing antibody response, whereas CD8+ T cells mainly mediated viral clearance from infected tissues. The difference in T cell immunity between Y and PS was primarily attributed to CD4+ T cells; adoptive transfer of Y-specific CD4+ T cells resulted in significantly enhanced protective ability, neutralizing antibody response, and viral clearance from the brain relative to PS-specific CD4+ T cells. Further investigations with chimeric viruses, mutant viruses, and their parental viruses identified two mutations (T151A and R304M) in the envelope (E) protein that contributed significantly to TMUV-specific CD4+ T cell-mediated protective ability and neutralizing antibody response, with more beneficial effects being conferred by R304M. These data indicate T cell-mediated immunity is important for protection from disease, for viral clearance from tissues, and for the production of neutralizing antibodies, and that the difference in CD4+T cell immunity between high- and low-virulence TMUV strains is primarily related to residues 151 and 304 in the E protein.

Pathogenesis of Cluster 1 Duck Tembusu Virus in Ducks Reveals the Impact of Viral Genotype on Pathogenicity and Disease Severity

“…The difference in the pathogenicity and disease severity between these two clusters may be partly associated with the variation in inducing host immune responses, particularly cellular immune responses. A previous study showed that highly virulent DTMUV elicited stronger cellular immune response than low virulent DTMUV, whereas both of them induced comparable levels of neutralizing antibodies [14]. Additional studies are required to clarify the role of host immune responses on the pathogenicity and virulence differences between cluster 1 and 2.1 DTMUVs.…”

“…The viral strain/genotype is believed to be one of the most important factors affecting the virulence and pathogenicity of DTMUV [12][13][14]. Most of the DTMUV pathogenesis evaluation has mainly focused on cluster 2, while information on the pathogenesis of other DTMUV clusters, particularly cluster 1, is limited.…”

“…However, the severity of the disease varies greatly from mild to severe clinical symptoms depending on several factors, including the age of duck, the strain of virus, the route of infection, and the virus infectivity titer [10][11][12][13]. Besides the duck age, the viral strain/genotype is likely to be a key factor affecting the virulence and pathogenicity of DTMUV [12][13][14]. However, the pathogenesis evaluation of DTMUV has been mainly restricted to cluster 2.…”