An Overlooked Protein Domain, WIV, Is Found a Wide Number of Arthropod Viruses and Probably Facilitates Infection

Abstract

Today, the most powerful approach to detect distant homologs of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we developed a powerful sequence-based procedure to identify distant homologs of viral proteins. It relies on 3 main principles: 1) Traces of sequence similarity with a protein can persist beyond the significance cutoff of homology detection programs; 2) Candidate homologs can be identified among proteins with weak sequence similarity to the query, by using "contextual" information, e.g. taxonomy or type of host infected; 3) These candidate homologs can be validated using highly sensitive profile-profile comparison.As a test case, we applied our approach to a protein without known homologs, ORF4 of Lake Sinai virus (which infects bees). We discovered that ORF4 is composed of a domain that has homologs in proteins from >20 taxa of viruses infecting arthropods. We called it “Widespread, Intriguing, Versatile” (WIV) domain because it is found in proteins with a wide variety of domain organizations and functions. For example, WIV is encoded by the NSs protein of tospoviruses, a global threat to food security, which infect plants through arthropod vectors; by the protein encoded by RNA2 ORF1 of chronic bee paralysis virus, a widespread virus of bees; and by various proteins of cypoviruses, which infect the silkworm bombyx mori. WIV has a previously unknown structural fold, according to Alphafold predictions. In some viral species, WIV facilitates infection of arthropods, according to bibliographical evidence

WIV, a protein domain found in a wide number of arthropod viruses, which probably facilitates infection

“…The recently discovered SPD-like domain, of unknown function, is similar to the small protrusion domain (SPD) of cypovirus 1 capsid protein VP1; see Fig. 7 of [41];…”

“…The SPD-like domain, found in some cypoviral proteins (d) has been discovered recently and is described elsewhere (see Fig. 7 of [41]).…”

“…The SPD-like domain, found in some cypoviral proteins (d) has been discovered recently and is described elsewhere (see Fig. 7 of [41]). best DALI hit], composed of a six-stranded β-sheet buttressed by three α-helices (Fig.…”

“…The recently discovered SPD-like domain, of unknown function, is similar to the small protrusion domain (SPD) of cypovirus 1 capsid protein VP1; see Fig. 7 of [41]; • An SPD-like domain followed by a poly ADP-ribose glycohydrolase (PARG) domain in the P5 protein of cypovirus 5 (and in the P5 protein of hubei lepidoptera virus 3, not shown in Fig. 2d); • An unknown domain (s) in the P8 protein of cypovirus 4, 14 and 23.…”

Prevalence and genome features of lake sinai virus isolated from Apis mellifera in the Republic of Korea

“…The capsid region (ORF3) plays a crucial role in the virus lifecycle, as it recognizes the host and assembles the virus capsid [ 19 ]. Meanwhile, the NS2 region (ORF4) can potentially facilitate infection in arthropod hosts, but its specific role remains under investigation [ 21 ]. Continuous molecular surveys are underway to assess the relative conservation of various LSV strains due to the significant diversity observed among them.…”