Investigation of clade B New World arenavirus tropism by using chimeric GP1 proteins.

Clade B of the New World arenaviruses contains both pathogenic and nonpathogenic members, whose surface glycoproteins (GPs) are characterized by different abilities to use the human transferrin receptor type 1 (hTfR1) protein as a receptor. Using closely related pairs of pathogenic and nonpathogenic viruses, we investigated the determinants of the GP1 subunit that confer these different characteristics. We identified a central region (residues 85 to 221) in the Guanarito virus GP1 that was sufficient to interact with hTfR1, with residues 159 to 221 being essential.

New world clade B arenaviruses can use transferrin receptor 1 (TfR1)-dependent and -independent entry pathways, and glycoproteins from human pathogenic strains are associated with the use of TfR1.

Arenaviruses are rodent-borne viruses, with five members of the family capable of causing severe hemorrhagic fevers if transmitted to humans. To date, two distinct cellular receptors have been identified that are used by different pathogenic viruses, alpha-dystroglycan by Lassa fever virus and transferrin receptor 1 (TfR1) by certain New World clade B viruses. Our previous studies have suggested that other, as-yet-unknown receptors are involved in arenavirus entry.

Receptor use by the Whitewater Arroyo virus glycoprotein.

Whitewater Arroyo virus (WWAV) is a North American New World arenavirus, first isolated from rats in New Mexico in 1993, and tentatively associated with three human fatalities in California in 1999-2000. However, it remains unclear whether WWAV was the cause of these, or any other, human infections. One important characteristic of viruses that influences pathogenic potential is the choice of cellular receptor and the corresponding tropism of the virus.