A STRUCTURAL CORRELATION BETWEEN LENTIVIRUS TRANSMEMBRANE PROTEINS AND NATURAL CYTOLYTIC PEPTIDES

Although oncoviruses and lentiviruses replicate by similar mechanisms, they differ fundamentally in the usual fate of the infected host cell during productive natural infections. Oncoviruses typically establish persistent nonlytic infections in natural host cells, while lentivirus infections characteristically result in a variety of cytopathic effects ultimately leading to death of the target cell. Described here is a unique structural motif consisting of a strongly amphipathic and arginine-rich helical peptide segment in the carboxyl end of lentivirus TM proteins that is structurally similar to the family of cytolytic peptides produced as defensive agents by certain insects and amphibians. Also demonstrated is the lytic nature of synthetic peptides constructed from the transmembrane (TM) protein of human and simian immunodeficiency viruses (HIV and SIV). Thus, it appears that the cytopathic properties of lentiviruses may be in part attributed to the presence of lytic peptides within the TM protein, designated lentivirus lytic peptide (LLP) and that variations in this segment could account for some of the differences observed in the cytopathicity among variants of a particular lentivirus.