The entry of Junin virus into Vero cells

Abstract

The entry mechanism of Junin virus (JV) into Vero cells was studied analyzing the effect of lysosomotropic compounds and acid pH on JV infection. Ammonium chloride, amantadine, chlorpheniramine and procaine inhibited JV production. The action of ammonium chloride was exerted at early times of infection. Virus internalization was inhibited and viral protein expression was not detected. When the extracellular medium was buffered at low pH, the ammonium chloride induced block on JV infection was overcome. Furthermore, JV was able to induce fusion of infected cells at pH 5.5 leading to polykaryocyte formation. Taken together, these results demonstrate that JV entry occurs through an endocytic mechanism requiring a low pH dependent membrane fusion.

Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses

“…Several properties of TfR1 support its critical role in arenaviral replication and disease. It is rapidly and constitutively internalized by clathrin-mediated endocytosis into an acidic compartment, consistent with the pathway and pH dependence of arenavirus cell entry (23,29). It is expressed ubiquitously and is expressed at high levels on activated or rapidly dividing cells, including macrophages and activated lymphocytes, which are major targets of arenaviruses in vivo (30)(31)(32)(33).…”

“…As with other class I fusion proteins, the GP1 subunit associates with a cellular receptor (17)(18)(19)(20). The GP2 subunit is a transmembrane protein that mediates fusion of the viral and cellular membranes after internalization of the virus into acidified endosomes (21)(22)(23)(24).…”

Unique Small Molecule Entry Inhibitors of Hemorrhagic Fever Arenaviruses

“…Upon internalization by endocytosis, arenaviruses are delivered to endosomes, where the viruses enter the cytoplasm by pH-induced GPmediated fusion of the viral and endosomal membranes (26,30). To determine the effect of the compounds 8C1 and 17C8 on arenavirus GP-mediated membrane fusion, we used a cellular fusion reporter assay (22).…”

Substitutions in the Glycoprotein (GP) of the Candid#1 Vaccine Strain of Junin Virus Increase Dependence on Human Transferrin Receptor 1 for Entry and Destabilize the Metastable Conformation of GP

“…Two different cellular receptors have been described, ␣-dystroglycan for the Old World and New World clade C viruses (10,30,38) and transferrin receptor type 1 (TfR1) for the New World clade B viruses (35). Binding of GP1 to a receptor results in endocytosis of the viral particle, where exposure to low pH triggers a series of conformational changes in GP2 that lead to fusion (7,11,25).…”