Early events in infection with arenaviruses
Lysosomotropic agents, weak bases and ionophores, were used to study the mode of penetration of arenaviruses into cells. All drugs studied (ammonium chloride, chloroquine, amantadine, monensin) effectively inhibited replication of Pichinde, Mopeia, and Lassa viruses in BHK-21 and Vero cells. The experimental results indirectly indicate that endocytosis, using acid cellular endosomes, is a mode of entry of arenaviruses into cells. For prediction of arenavirus fusion protein we used an analysis of the elements of secondary and tertiary structure of precursor proteins of glycoproteins of five members of this virus family. Two regions of protein GP2 possessed properties that satisfied our criteria for selection of fusion peptides of enveloped viruses. One of the selected peptides was synthesized and model biophysical experiments demonstrated its ability to interact with lipid and to form single ion channels in the planar lipid bilayers, typical of fusion proteins of enveloped viruses. These data suggest that protein GP2 is the fusion protein of arenaviruses and that the fusion peptide is located in the immediate proximity to the N-end of this polypeptide.
KeywordsVero Cell Ammonium Chloride Envelop Virus Fusion Peptide Planar Lipid Bilayer
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- 3.Auperin DD, McCormick JB (1989) Nucleotide sequence of the Lassa virus ( Josiah strain) S genome RNA and amino acid sequence comparison of the N and GPC proteins to other arenaviruses. Virology 168: 421–425Google Scholar
- 10.Hladky SB, Haydon DA (1972) Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies of the unit conductance channel. Biochim Biophys Acta 274: 294–312Google Scholar
- 18.Romanowski V, Bishop DHL (1985) Conserved sequences and coding of two strains of lymphocytic choriomeningitis virus ( WE and ARM) and Pichinde arenavirus. Virus Res 2: 35–51Google Scholar
- 19.Romanowski V, Matsuura Y, Bishop DHL (1985) Complete sequence of the S RNA of lymphocytic choriomeningitis virus ( WE strain) compared to that of Pichinde arena-virus. Virus Res 3: 101–114Google Scholar
- 21.Spear PG (1987) Virus-induced cell fusion. In: Sowers AE (ed) Cell fusion. Plenum, New York, pp 3–32Google Scholar