Emerging zoonotic viruses: new lessons on receptor and entry mechanisms

Viruses enter the host cell by binding cellular receptors that allow appropriate delivery of the viral genome. Although the horizontal propagation of viruses feeds the continuous emergence of novel pathogenic viruses, the genetic variation of cellular receptors can represent a challenging barrier. The SARS coronavirus, henipaviruses and filoviruses are zoonotic RNA viruses that use bats as their reservoir. Their lethality for man has fostered extensive research both on the cellular receptors they use and their entry pathways. These studies have allowed new insights into the diversity of the molecular mechanisms underlying both virus entry and pathogenesis.

► SARS-coronavirus is a rather unique example of a correlation between virus affinity to a cellular receptor, entry efficiency and receptor mediated-pathogenicity with involvement of an ectoprotease cleaving both envelope glycoprotein and receptor. ► Henipaviruses is exemplary in mimicking the binding of physiological ligand to their cellular receptors to enter mainly via macropinocytosis. ► Filoviruses use a long and complex entry pathway involving macropinocytosis, a postulated cellular receptor and a multistep activation of the envelope protein.