Entry of Rhabdoviruses Into Animal Cells

Abstract

Entry is the first step in the infectious life cycle of a virus. In the case of rhabdoviruses, entry is facilitated exclusively by the envelope glycoprotein G and its interactions with the host cell. For vesicular stomatitis virus (VSV), attachment to the cell surface was thought to be facilitated by interactions with the lipid phosphatidylserine, however recent work suggests that it is in fact initiated by recognition of proteinaeous receptors. Clathrin-mediated endocytosis delivers the virions into endosomes where they have been proposed to traffic to multi-vesicular bodies. There, the viral envelope fuses with internal vesicles in a process mediated by glycoprotein G in a pH- and phosphatidylserine-dependent manner. A clear mechanistic understanding of glycoprotein G mediated fusion has yet to be obtained, however current data suggests that it is likely facilitated by events distinct from Class I or Class II fusion proteins of other viruses. Rhabdoviruses are also notable in that their fusion protein exists in a reversible pH-dependent equilibrium, which prevents irreversible preactivation during assembly, and may prove to be relevant in the mediation of cell-to-cell fusion - an alternate form of viral spread.

The Microtubule Inhibitor Podofilox Inhibits an Early Entry Step of Human Cytomegalovirus

“…The viruses for which podofilox has low EC 50 values and high MP—AD169 and HSV1—all engage receptors in a multi-step process prior to lipid fusion at the cell surface [15,45,46]; whereas IAV, NDV, and SeV—the viruses resistant to podofilox—engage putative sialic acid based receptors in a single step prior to lipid fusion [47,48,49]. Between those two phenotypes are TB40/E and VSV, viruses that engage receptors in a multistep process prior to lipid fusion in an endosome [20,50]. Collectively, podofilox inhibition of microtubules defines the requirement of the cytoskeleton network for virus to gain entry into cells.…”

“…The multistep entry process for the α-herpesvirus HSV1 [45] is similar to CMV, a β-herpesvirus and thus, the efficacy of podofilox is also very similar (EC 50 of 20 nM vs. 26 nM [26], respectively). VSV also engages multiple receptors prior to entry [50] and has a low EC 50 value of 24 nM. Yet, VSV is different from HSV1 by nature of entering the cell via pH dependent endocytosis instead of fusion at the cell surface, and is not fully inhibited by podofilox (MPI 68% vs. 90% for HSV1).…”

Infectious bronchitis virus entry mainly depends on clathrin mediated endocytosis and requires classical endosomal/lysosomal system

“…The actin cytoskeleton machinery is recruited after coat formation and provides an essential force for membrane deformation and internalization (Kaksonen et al, 2005). Recent studies have revealed that the rhabdoviruses (Regan and Whittaker, 2013), VSV (Cureton et al, 2010), RABV (Piccinotti et al, 2013), and IHNV (Liu et al, 2011) are internalized into cells via CME pathway and actin filaments are involved in. Although we have demonstrated that IBV enter cells by hijacking clathrin dependent route, it is unclear whether actin filaments are involved in IBV uptake.…”

Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives

“…To infect a cell, a virion must attach itself to the cell surface. This can occur via ancillary attachment factors or directly via the major receptor used by the virus for entry; some viruses then interact with a second receptor, or coreceptor [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79]. Naked viruses need to penetrate a cellular membrane to enter the cytoplasm or instead they may inject their genome through a membrane [80]; enveloped viruses must fuse their envelope with a cellular membrane in order to translocate their core and genome into the cytoplasm [79,[81][82][83][84][85].…”