Proteomic and Phosphoproteomic Analyses Reveal Gibel Carp Responses to Cyprinid Herpesvirus 2 Infection

Cyprinid herpesvirus 2 (CyHV-2) is
a typical linear double-stranded
DNA virus, which can induce severe herpesviral hematopoietic necrosis
disease (HVHND) in gibel carp. However, the CyHV-2 infection mechanisms
still remain unresolved till now. Here, we combined the isobaric tag
for relative absolute quantitation (iTRAQ)-labeled quantitative proteomic
and phosphoproteomic analysis enriched by Ti4+-immobilized
titanium ion affinity chromatography (IMAC) to uncover the host responses
to CyHV-2 infection in the kidneys of symptomatic and diseased gibel
carp. We totally identified 192 differential expression proteins and
951 high-confident phosphopeptides involved in 657 proteins. After
being infected with CyHV-2, the proteins involved in energy generation
and ion balance were significantly downregulated in the host, and
the phosphorylated proteins induced by viral infection mainly participated
in the regulation for RNA processing, translation, cytoskeleton organization,
immunoreaction, etc. Furthermore, 11 phosphorylated
CyHV-2 viral proteins were found in the diseased group by the host
proteome. The virus–host protein–protein interactions
were investigated, in which the potential host kinases casein kinase
II (CK-II) and cyclin-dependent kinase (CDK) that interacted with
viral ORF88 or ORF89 were identified and can serve as candidate targets
for disease treatment in the future. Overall, our study provides a
comprehensive understanding of CyHV-2-induced perturbations at the
protein and phosphorylation levels in gibel carp, forming a base for
the treatment of HVHND.