AlphaFold modeling of the white spot syndrome virus polymerase

Abstract

White spot syndrome virus (WSSV) infects crustaceans, causing severe losses in the global shrimp industry. Several properties, including the DNA genome sequence and the virion morphology, place WSSV as the single member of the Whispovirus genus of the Nimaviridae family. The DNA polymerase is one of the few gene products of the predicted 184 open reading frames to have been examined. Conserved sequence motifs found in many viral DNA polymerases are found in the WSSV DNA polymerase; nevertheless, the WSSV enzyme remains enigmatic, possessing over 1000 amino acids more than, for example, the DNA polymerase of herpes simplex virus 1 (HSV- 1). To examine more closely the WSSV polymerase, we used AlphaFold to generate a structural model and compared it to the DNA polymerases of HSV-1, African swine fever virus and mpox virus. The exonuclease and polymerase domains of the WSSV enzyme were exactly defined based on the equivalence with the other viral enzymes; structurally, the WSSV enzyme appears most closely related to the HSV-1 enzyme. In contrast, the WSSV polymerase N-terminal domain showed an appreciably different architecture. However, the most unusual aspect of the WSSV polymerase is the C-terminal thumb domain which is modelled as two helical domains connected by a flexible acidic loop. This arrangement is quite unrelated to the thumb domains found in the other polymerases and is thus restricted to the WSSV enzyme. Given the uniqueness of such a vital cog of the repli cation machinery, it will be of interest to examine the structures of further WSSV proteins. (248 words).