title: Hijacking of host calreticulin is required for the white spot syndrome virus replication cycle.
abstract: We have previously shown that multifunctional calreticulin (CRT), which resides in the endoplasmic reticulum (ER) and is involved in ER-associated protein processing, responds to infection with white spot syndrome virus (WSSV) by increasing mRNA and protein expression and by forming a complex with gC1qR and thereby delaying apoptosis. Here, we show that CRT can directly interact with WSSV structural proteins, including VP15 and VP28, during an early stage of virus infection. The binding of VP28 with CRT does not promote WSSV entry, and CRT-VP15 interaction was detected in the viral genome in virally infected host cells and thus may have an effect on WSSV replication. Moreover, CRT was detected in the viral envelope of purified WSSV virions. CRT was also found to be of high importance for proper oligomerization of the viral structural proteins VP26 and VP28, and when CRT glycosylation was blocked with tunicamycin, a significant decrease in both viral replication and assembly was detected. Together, these findings suggest that CRT confers several advantages to WSSV, from the initial steps of WSSV infection to the assembly of virions. Therefore, CRT is required as a "vital factor" and is hijacked by WSSV for its replication cycle. Importance: White spot syndrome virus (WSSV) is a double-stranded DNA virus and the cause of a serious disease in a wide range of crustaceans that often leads to high mortality rates. We have previously shown that the protein calreticulin (CRT), which resides in the endoplasmic reticulum (ER) of the cell, is important in the host response to the virus. In this report, we show that the virus uses this host protein to enter the cell and to make the host produce new viral structural proteins. Through its interaction with two viral proteins, the virus "hijacks" host calreticulin and uses it for its own needs. These findings provide new insight into the interaction between a large DNA virus and the host protein CRT and may help in understanding the viral infection process in general.
authors.affiliation: Department of Comparative Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Apiruck
authors.initials: A
authors.lastname: Watthanasurorot
authors.affiliation: Department of Comparative Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Enen
authors.initials: E
authors.lastname: Guo
authors.affiliation: Department of Veterinary Technology, Faculty of Veterinary Technology, Kasetsart University, Bangkok, Thailand.
authors.forename: Sirinit
authors.initials: S
authors.lastname: Tharntada
authors.affiliation: College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors.forename: Chu-Fang
authors.initials: CF
authors.lastname: Lo
authors.affiliation: Department of Comparative Physiology, Uppsala University, Uppsala, Sweden Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Söderhäll
authors.affiliation: Department of Comparative Physiology, Uppsala University, Uppsala, Sweden Irene.Soderhall@ebc.uu.se.
authors.forename: Irene
authors.initials: I
authors.lastname: Söderhäll
mesh_terms: D000818:Animals; D003400:Astacoidea; D037282:Calreticulin / Q000378:metabolism*; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D011485:Protein Binding; D014759:Viral Envelope Proteins / Q000378:metabolism*; D019065:Virus Assembly; D014779:Virus Replication; D046848:White spot syndrome virus 1 / Q000502:physiology*
chemical_list: D037282:Calreticulin; D019590:Nucleocapsid Proteins; C446942:VP15 protein, white spot syndrome virus; C548473:VP28 protein, white spot syndrome virus; D014759:Viral Envelope Proteins