Salmonid viral haemorrhagic septicaemia virus: fusion-related enhancement of virus infectivity by peptides derived from viral glycoprotein G or a combinatorial library

Abstract

To search for enhancers and/or inhibitors of viral haemorrhagic septicaemia virus (VHSV, a salmonid rhabdovirus) infectivity, a total of 51 peptides from a pepscan of viral envelope protein G, a recombinant peptide from protein G (frg11) and 80 peptide mixtures from an α-helix-favoured combinatorial library were screened. However, contrary to what occurs in many other enveloped viruses, only peptides enhancing rather than inhibiting VHSV infectivity were found. Because some of the enhancer pepscan G peptides and frg11 were derived from phospholipid-binding or fusion-related regions identified previously, it was suggested that enhancement of virus infectivity might be related to virus–cell fusion. Furthermore, enhancement was significant only when the viral peptides were pre-incubated with VHSV at the optimal low pH of fusion, before being adjusted to physiological pH and assayed for infectivity. Enhancement of VHSV infectivity caused by the pre-incubation of VHSV with peptide p5 (SAAEASAKATAEATAKG), one of the individual enhancer peptides defined from the screening of the combinatorial library, was independent of the pre-incubation pH. However, it was also related to fusion because the binding of p5 to protein G induced VHSV to bypass the endosome pathway of infection and reduced the low-pH threshold of fusion, thus suggesting an alternative virus entry pathway for p5–VHSV complexes. Further investigations into VHSV enhancer peptides might shed some light on the mechanisms of VHSV fusion.