Entry of Bunyaviruses into Mammalian Cells

Abstract

The Bunyaviridae constitute a large family of enveloped animal viruses, many members of which cause serious diseases. However, early bunyavirus-host cell interactions and entry mechanisms remain largely uncharacterized. Investigating Uukuniemi virus, a bunyavirus of the genus Phlebovirus, we found that virus attachment to the cell surface was specific but inefficient, with 25% of bound viruses being endocytosed within 10 min, mainly via noncoated vesicles. The viruses entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomes. Acid-activated penetration, occurring 20-40 min after internalization, required maturation of early to late endosomes. The pH threshold for viral membrane fusion was 5.4, and entry was sensitive to temperatures below 25 degrees C. Together, our results indicate that Uukuniemi virus penetrates host cells by acid-activated membrane fusion from late endosomal compartments. This study also highlights the importance of the degradative branch of the endocytic pathway in facilitating entry of late-penetrating viruses.

Vaccinia Virus Infection Requires Maturation of Macropinosomes

“…In addition, there is conversion of phosphatidylinositol 3‐phosphate (PtdIns(3)P) to PtdIns(3,5)P 2 , and progressive luminal acidification 7, 8, 9, 10, 11. As virus penetration and uncoating relies on the environment within maturing endosomes, it is perhaps no surprise that for many viruses, infection depends on factors involved in the maturation process 12, 13, 14.…”

<b>The amino acid at position 624 in the glycoprotein of SFTSV (severe fever with thrombocytopenia virus) plays a critical role in low-pH-dependent cell fusion </b><b>activity </b>

“…In addition, GP-Y/S and GP-Y/D also induced cell fusion in transfected cells. RVFV and UUKV have a serine and an aspartic acid, respectively, at the site corresponding to position 624 in SFTSV, and both viruses also induce formation of syncytia over a pH range below pH 6.2 or 5.8, respectively (9,15). The pH ranges for cell fusion of RVFV and UUKV were the same as those for SFSTV GP-Y/S and GP-Y/D, suggesting that the amino acid at position 624 plays a role in determining the sensitivity of phlebovirus GPs to low pH conditions.…”

“…SFTSV attaches to host cell receptors and is endocytosed in a receptor-mediated manner. Acidification of the endocytic vesicle triggers a conformational change in GP, which then facilitates the fusion of the viral envelope with the vesicle membrane (15,22,26). In a recent study, the crystal structure of Gc was solved, and several amino acids were determined to be key factors for the pCAGGS-MCS plasmid vector (pCSFTSV-GP).…”

DC-SIGN, un récepteur des phlébovirus

“…À ces valeurs, l'acidité provoque la dissociation des tétramères de DC-SIGN en monomères qui ont une faible affinité pour leurs substrats [11]. Alors que la lectine est probablement recyclée vers la surface, les virus poursuivent leur route vers les endosomes tardifs où le pH (5,0-6,0) permet la fusion membranaire des particules virales (Figure 1) [10,12].…”