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 alpha-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.