Entry of Phenuiviruses into Mammalian Host Cells

Abstract

Phenuiviridae is a large family of arthropod-borne viruses with over 100 species worldwide. Several cause severe diseases in both humans and livestock. Global warming and the apparent geographical expansion of arthropod vectors are good reasons to seriously consider these viruses potential agents of emerging diseases. With an increasing frequency and number of epidemics, some phenuiviruses represent a global threat to public and veterinary health. This review focuses on the early stage of phenuivirus infection in mammalian host cells. We address current knowledge on each step of the cell entry process, from virus binding to penetration into the cytosol. Virus receptors, endocytosis, and fusion mechanisms are discussed in light of the most recent progress on the entry of banda-, phlebo-, and uukuviruses, which together constitute the three prominent genera in the Phenuiviridae family.

Highly adaptive Phenuiviridae with biomedical importance in multiple fields

“…One phenuivirus may employ two or more internalization pathways. For instance, RVFV can employ caveolin-mediated endocytosis and caveolin-independent micropinocytosis [93]. Ribonuclease kappa promotes the internalization of some phenuiviruses [103].…”

“…The cytoplasmic tail of phlebovirus Gc proteins is short (e.g., only five amino acid residues for UUKV), while the cytoplasmic tail of Gn is much longer (e.g., 81 amino acid residues for UUKV) [50]. The extended length is associated with additional biological functions: the Gn cytoplasmic tail contains the Golgi localization signal and initiates the budding process and packaging RNPs into virus particles [93].…”

Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells

“…The underlying cellular mechanisms could vary considerably in different target cells. As recently discussed for phleboviruses [ 58 ], the ability of OBVs to use alternative receptors on the cell surface very likely impacts their capacity to enter one or more endocytic pathways to infect cells and tissues.…”

“…This process occurs along with major changes in proteins, lipids, and proton (H + ) concentrations in endosomal vesicles [ 61 ]. The intraluminal pH decreases from ~6.5 in EEs to ~5.5–5.0 in LEs [ 58 ]. Several reports have demonstrated that OBVs depend on endosomal acidification for infection [ 62 ].…”

Highly Adaptive <em>Phenuiviridae</em> with Great Biomedical Importance

“…After the budding of new virus particles from the Golgi, virus-containing vesicles are transported to the plasma membrane, where the virions are released via exocytosis [50]. Some phenuiviruses (e.g., SFTSV) may be efficiently delivered to uninfected cells through extracellular vesicles in receptor-independent exocytosis machinery [93].…”