Functional tolerance of the human immunodeficiency virus type 1 envelope signal peptide to mutations in the amino-terminal and hydrophobic regions.

We demonstrated that the leader sequence of the human immunodeficiency virus type 1 envelope functions as signal peptide (SP) despite low scoring in a prediction program. As expected for SP, the hydrophobic core (HC) is essential, and no other sequence could compensate for HC deletion. Contrary to other SPs, major substitutions in the HC, such as introduction of basic, polar, or alpha-helix-breaking residues, still allowed efficient translocation and glycosylation. Also, extensive deletions or substitutions of the charged residues at the N terminus had little if any inhibitory effect. This report, which is the first study of human immunodeficiency virus SP, describes the exceptional tolerance of this peptide to mutations.