Co-infection of nervous necrosis virus and Vibrio harveyi increased mortality and worsened the disease severity in the orange-spotted grouper (Epinephelus coioides)

Lingfeng Guan; Xinshuai Li; Jinpeng Chen; Liqun Wang; Xinyue Zhang; Hongyan Sun; Yanwei Li; Min Yang; Qiwei Qin; Shaowen Wang

doi:10.1016/j.fsi.2025.110117

Co-infection of nervous necrosis virus and Vibrio harveyi increased mortality and worsened the disease severity in the orange-spotted grouper (Epinephelus coioides)

Fish Shellfish Immunol. 2025 Jan 8:110117. doi: 10.1016/j.fsi.2025.110117. Online ahead of print.

Authors

Affiliations

¹ College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
² College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, 511464, China. Electronic address: yangmin2016@scau.edu.cn.
³ College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, 511464, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai 519000, China. Electronic address: qinqw@scau.edu.cn.
⁴ College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, 511464, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address: wangsw@scau.edu.cn.

PMID: 39793911
DOI: 10.1016/j.fsi.2025.110117

Abstract

Co-infections of different pathogenic microorganisms usually cause complex effects, and receive more attention. Red-grouper nervous necrosis virus (RGNNV) and Vibrio are the common viral and bacterial pathogens of fish, and are often detected simultaneously in diseased fish. However, the understanding of co-infection of RGNNV and Vibrio is still unclear. In this study, we have established a grouper (Epinephelus coioides) model of the co-infection of RGNNV and Vibrio harveyi (V. harveyi). Compared with single pathogen infection, co-infection of RGNNV and V. harveyi significantly caused more severe pathologic changes with higher mortality (P<0.05), and promoted the proliferation of the pathogens by RNA-FISH and qRT-PCR (P<0.05), demonstrating a synergistic effect of RGNNV and V. harveyi in grouper. Furthermore, we found that V. harveyi inhibited the induction and migration of neutrophils by RGNNV, resulting the obviously reduced neutrophils of co-infection groups (P<0.05). In addition, transcriptome analysis showed that differentially expressed genes (DEGs) of brain tissues of different experimental groups were enriched in immune signaling pathways, such as JAK-STAT signaling, NF-κB signaling and TNF signaling pathways. For the liver and spleen tissues, the DEGs of different experimental groups were enriched in metabolism-related pathways, such as glycolysis/gluconeogenesis and glycerolipid metabolism. Further analysis of the selected DEGs, co-infection of RGNNV and V. harveyi significantly suppressed the host immune response and up-regulated host glucose and lipid metabolism, compared with single-pathogen infection. Taken together, the RGNNV and V. harveyi make synergic reaction in grouper, possibly due to the down regulation of host immune response and up regulation of metabolism to facilitate the replication of both pathogens. These results provide new insights into the pathogenesis of multiple pathogens, and contribute to develop new therapies.

Keywords: Grouper; Red-grouper nervous necrosis virus; Synergistic effect; Vibrio harveyi.